Publications

Abstract

In this study data from the first six months of 12 children s multiword speech were used to test the validity of Valian's (1991) syntactic perfor-mance-limitation account and Tomasello s (1992) verb-island account of early multiword speech with particular reference to the development of the English verb category. The results provide evidence for appropriate use of verb morphology, auxiliary verb structures, pronoun case marking, and SVO word order from quite early in development. However, they also demonstrate a great deal of lexical specificity in the children's use of these systems, evidenced by a lack of overlap in the verbs to which different morphological markers were applied, a lack of overlap in the verbs with which different auxiliary verbs were used, a disproportionate use of the first person singular nominative pronoun I, and a lack of overlap in the lexical items that served as the subjects and direct objects of transitive verbs. These findings raise problems for both a syntactic performance-limitation account and a strong verb-island account of the data and suggest the need to develop a more general lexiealist account of early multiword speech that explains why some words come to function as "islands" of organization in the child's grammar and others do not.

Abstract

In a recent series of papers, Caramazza and Miozzo [Caramazza, A., 1997. How many levels of processing are there in lexical access? Cognitive Neuropsychology 14, 177-208; Caramazza, A., Miozzo, M., 1997. The relation between syntactic and phonological knowledge in lexical access: evidence from the 'tip-of-the-tongue' phenomenon. Cognition 64, 309-343; Miozzo, M., Caramazza, A., 1997. On knowing the auxiliary of a verb that cannot be named: evidence for the independence of grammatical and phonological aspects of lexical knowledge. Journal of Cognitive Neuropsychology 9, 160-166] argued against the lemma/lexeme distinction made in many models of lexical access in speaking, including our network model [Roelofs, A., 1992. A spreading-activation theory of lemma retrieval in speaking. Cognition 42, 107-142; Levelt, W.J.M., Roelofs, A., Meyer, A.S., 1998. A theory of lexical access in speech production. Behavioral and Brain Sciences, (in press)]. Their case was based on the observations that grammatical class deficits of brain-damaged patients and semantic errors may be restricted to either spoken or written forms and that the grammatical gender of a word and information about its form can be independently available in tip-of-the-tongue stales (TOTs). In this paper, we argue that though our model is about speaking, not taking position on writing, extensions to writing are possible that are compatible with the evidence from aphasia and speech errors. Furthermore, our model does not predict a dependency between gender and form retrieval in TOTs. Finally, we argue that Caramazza and Miozzo have not accounted for important parts of the evidence motivating the lemma/lexeme distinction, such as word frequency effects in homophone production, the strict ordering of gender and pho neme access in LRP data, and the chronometric and speech error evidence for the production of complex morphology.

Abstract

According to most models of speech production, the planning of spoken words involves the independent retrieval of segments and metrical frames followed by segment-to-frame association. In some models, the metrical frame includes a specification of the number and ordering of consonants and vowels, but in the word-form encoding by activation and verification (WEAVER) model (A. Roelofs, 1997), the frame specifies only the stress pattern across syllables. In 6 implicit priming experiments, on each trial, participants produced 1 word out of a small set as quickly as possible. In homogeneous sets, the response words shared word-initial segments, whereas in heterogeneous sets, they did not. Priming effects from shared segments depended on all response words having the same number of syllables and stress pattern, but not on their having the same number of consonants and vowels. No priming occurred when the response words had only the same metrical frame but shared no segments. Computer simulations demonstrated that WEAVER accounts for the findings.

Abstract

This article reports 7 experiments investigating whether utterances are planned in a parallel or rightward incremental fashion during language production. The experiments examined the role of linear order, length, frequency, and repetition in producing Dutch verb–particle combinations. On each trial, participants produced 1 utterance out of a set of 3 as quickly as possible. The responses shared part of their form or not. For particle-initial infinitives, facilitation was obtained when the responses shared the particle but not when they shared the verb. For verb-initial imperatives, however, facilitation was obtained for the verbs but not for the particles. The facilitation increased with length, decreased with frequency, and was independent of repetition. A simple rightward incremental model accounts quantitatively for the results.

Abstract

To investigate the role of the syllable in Dutch speech production, five experiments were carried out to examine the effect of visually masked syllable primes on the naming latencies for written words and pictures. Targets had clear syllable boundaries and began with a CV syllable (e.g., ka.no) or a CVC syllable (e.g., kak.tus), or had ambiguous syllable boundaries and began with a CV[C] syllable (e.g., ka[pp]er). In the syllable match condition, bisyllabic Dutch nouns or verbs were preceded by primes that were identical to the target’s first syllable. In the syllable mismatch condition, the prime was either shorter or longer than the target’s first syllable. A neutral condition was also included. None of the experiments showed a syllable priming effect. Instead, all related primes facilitated the naming of the targets. It is concluded that the syllable does not play a role in the process of phonological encoding in Dutch. Because the amount of facilitation increased with increasing overlap between prime and target, the priming effect is accounted for by a segmental overlap hypothesis.

Abstract

This article discusses how the Trobriand Islanders speak about body and mind. It addresses the following questions: do the linguistic datafit into theories about lexical universals of body-part terminology? Can we make inferences about the Trobrianders' conceptualization of psychological and physical states on the basis of these data? If a Trobriand Islander sees these idioms as external manifestations of inner states, then can we interpret them as a kind of ethnopsychological theory about the body and its role for emotions, knowledge, thought, memory, and so on? Can these idioms be understood as representation of Trobriand ethnopsychological theory?

Abstract

A quantitative model of human categorization behavior is proposed, which can be applied to 4-alternative forced-choice categorization data involving two binary classifications. A number of processing dependencies between the two classifications are explicitly formulated, such as the dependence of the location, orientation, and steepness of the class boundary for one classification on the outcome of the other classification. The significance of various types of dependencies can be tested statistically. Analyses of a data set from the literature shows that interesting dependencies in human speech recognition can be uncovered using the model.

Abstract

This study investigates whether spoken sentence comprehension deficits in Broca's aphasics results from their inability to access the subordinate meaning of ambiguous words (e.g. bank), or alternatively, from a delay in their selection of the contextually appropriate meaning. Twelve Broca's aphasics and twelve elderly controls were presented with lexical ambiguities in three context conditions, each followed by the same target words. In the concordant condition, the sentence context biased the meaning of the sentence final ambiguous word that was related to the target. In the discordant condition, the sentence context biased the meaning of the sentence final ambiguous word that was incompatible with the target.In the unrelated condition, the sentence-final word was unambiguous and unrelated to the target. The task of the subjects was to listen attentively to the stimuli The activational status of the ambiguous sentence-final words was inferred from the amplitude of the N399 to the targets at two inter-stimulus intervals (ISIs) (100 ms and 1250 ms). At the short ISI, the Broca's aphasics showed clear evidence of activation of the subordinate meaning. In contrast to elderly controls, however, the Broca's aphasics were not successful at selecting the appropriate meaning of the ambiguity in the short ISI version of the experiment. But at the long ISI, in accordance with the performance of the elderly controls, the patients were able to successfully complete the contextual selection process. These results indicate that Broca's aphasics are delayed in the process of contextual selection. It is argued that this finding of delayed selection is compatible with the idea that comprehension deficits in Broca's aphasia result from a delay in the process of integrating lexical information.

Abstract

This volume on Inuit speech follows the evolution of a native language of the North American Arctic, from its historical roots to its present-day linguistic structure and patterns of use from Alaska to Greenland. Drawing on a wide range of research from the fields of linguistics, anthropology, and sociology, Dorais integrates these diverse perspectives in a comprehensive view of native language development, maintenance, and use under conditions of marginalization due to social transition.

Abstract

This work presents a salvage grammar of the Biri language of Eastern Central Queensland, a Pama-Nyungan language belonging to the large Maric subgroup. As the language is no longer used, the grammatical description is based on old written sources and on recordings made by linguists in the 1960s and 1970s. Biri is in many ways typical of the Pama-Nyungan languages of Southern Queensland. It has split case marking systems, marking nouns according to an ergative/absolutive system and pronouns according to a nominative/accusative system. Unusually for its area, Biri also has bound pronouns on its verb, cross-referencing the person, number and case of core participants. As far as it is possible, the grammatical discussion is ‘theory neutral’. The first four chapters deal with the phonology, morphology, and syntax of the language. The last two chapters contain a substantial discussion of Biri’s place in the Pama-Nyungan family. In chapter 6 the numerous dialects of the Biri language are discussed. In chapter 7 the close linguistic relationship between Biri and the surrounding languages is examined.

Abstract

In normal conversation, speakers translate thoughts into words at high speed. To enable this speed, the retrieval of distinct types of linguistic knowledge has to be orchestrated with millisecond precision. The nature of this orchestration is still largely unknown. This report presents dynamic measures of the real-time activation of two basic types of linguistic knowledge, syntax and phonology. Electrophysiological data demonstrate that during noun-phrase production speakers retrieve the syntactic gender of a noun before its abstract phonological properties. This two-step process operates at high speed: the data show that phonological information is already available 40 milliseconds after syntactic properties have been retrieved.

Abstract

Recent studies using phoneme detection tasks have shown that spoken-language processing is neither facilitated nor interfered with by optional assimilation, but is inhibited by violation of obligatory assimilation. Interpretation of these results depends on an assessment of their generality, specifically, whether they also obtain when listeners are processing nonnative language. Two separate experiments are presented in which native listeners of German and native listeners of Dutch had to detect a target fricative in legal monosyllabic Dutch nonwords. All of the nonwords were correct realisations in standard Dutch. For German listeners, however, half of the nonwords contained phoneme strings which violate the German fricative assimilation rule. Whereas the Dutch listeners showed no significant effects, German listeners detected the target fricative faster when the German fricative assimilation was violated than when no violation occurred. The results might suggest that violation of assimilation rules does not have to make processing more difficult per se.

Abstract

Children's gestures can reveal important information about their problem-solving strategies. This study investigated whether the information children express only in gesture is accessible to adults not trained in gesture coding. Twenty teachers and 20 undergraduates viewed videotaped vignettes of 12 children explaining their solutions to equations. Six children expressed the same strategy in speech and gesture, and 6 expressed different strategies. After each vignette, adults described the child's reasoning. For children who expressed different strategies in speech and gesture, both teachers and undergraduates frequently described strategies that children had not expressed in speech. These additional strategies could often be traced
to the children's gestures. Sensitivity to gesture was comparable for teachers and
undergraduates. Thus, even without training, adults glean information, not only from children's words but also from their hands.

Abstract

Are regular morphologically complex words stored in the mental lexicon? Answers to this question have ranged from full listing to parsing for every regular complex word. We investigated the roles of storage and parsing in the visual domain for the productive Dutch plural suffix -en.Two experiments are reported that show that storage occurs for high-frequency noun plurals. A mathematical formalization of a parallel dual-route race model is presented that accounts for the patterns in the observed reaction time data with essentially one free parameter, the speed of the parsing route. Parsing for noun plurals appears to be a time-costly process, which we attribute to the ambiguity of -en,a suffix that is predominantly used as a verbal ending. A third experiment contrasted nouns and verbs. This experiment revealed no effect of surface frequency for verbs, but again a solid effect for nouns. Together, our results suggest that many noun plurals are stored in order to avoid the time-costly resolution of the subcategorization conflict that arises when the -ensuffix is attached to nouns.

Abstract

In this paper, I present an analysis of the so-called tense forms of Biblical Hebrew. While there is fairly broad consensus on the interpretation of the yiqtol tense form, the interpretation of the qdtal tense form has led to considerable controversy. I will argue that the qātal form has no intrinsic semantic value and that it serves a pragmatic function only, namely, signaling to the hearer that the event or state expressed by the verb cannot be tightly integrated into the discourse representation of the hearer, given the speaker's estimate of their common ground.

Abstract

This paper addresses the relation between meaning, lexical productivity, and frequency of use. Using density estimation as a visualization tool, we show that differences in semantic structure can be reflected in probability density functions estimated for word frequency distributions. We call attention to an example of a bimodal density, and suggest that bimodality arises when distributions of well-entrenched lexical tems, which appear to be lognormal, are mixed with distributions of productively reated nonce formations

Abstract

The Basic Variety (BV) as conceived by Klein and Perdue (K&P) is a relatively stable state in the process of spontaneous (adult) second language acquisition, characterized by a small set of phrasal, semantic and pragmatic principles. These principles are derived by inductive generalization from a fairly large body of data. They are considered by K&P as roughly equivalent to those of Universal Grammar (UG) in the sense of Chomsky's Minimalist Program, with the proviso that the BV allows for only weak (or unmarked) formal features. The present article first discusses the viability of the BV principles proposed by K&P, arguing that some of them are in need of clarification with learner varieties, and that they are, in any case, not likely to be part of UG, as they exclude phenomena (e.g., so-called psych verbs) that cannot be ruled out even from the core of natural language. The article also considers the proposal that learner varieties of the BV type are completely unmarked instantiations of UG. Putting aside problems arising from the Minimalist Program, especially the question whether a grammar with only weak features would be a factual possibility and what it would look like, it is argued that the BV as characterized by K&P must be considered as the result of a process that crucially differs from first language acquisition as furnished by UG for a number of reasons, including properties of the BV itself. As a matter of fact, several of the properties claimed for the BV by K&P are more likely the result of general learning strategies than of language-specific principles. If this is correct, the characterization of the BV is a fairly interesting result, albeit of a rather different type than K&P suggest.

Abstract

The notion of relational grammar is extented to ternary relations and illustrated by a fragment of English. Some of Peirce's terms for ternary relations are shown to be incorrect and corrected.

Abstract

How do children isolate the semantic package contained in verb roots in the Mayan language Tzeltal? One might imagine that the canonical CVC shape of roots characteristic of Mayan languages would make the job simple, but the root is normally preceded and followed by affixes which mask its identity. Pye (1983) demonstrated that, in Kiche' Mayan, prosodic salience overrides semantic salience, and children's first words in Kiche' are often composed of only the final (stressed) syllable constituted by the final consonant of the CVC root and a 'meaningless' termination suffix. Intonation thus plays a crucial role in early Kiche' morphological development. Tzeltal presents a rather different picture: The first words of children around the age of 1;6 are bare roots, children strip off all prefixes and suffixes which are obligatory in adult speech. They gradually add them, starting with the suffixes (which receive the main stress), but person prefixes are omitted in some contexts past a child's third birthday, and one obligatory aspectual prefix (x-) is systematically omitted by the four children in my longitudinal study even after they are four years old. Tzeltal children's first verbs generally show faultless isolation of the root. An account in terms of intonation or stress cannot explain this ability (the prefixes are not all syllables; the roots are not always stressed). This paper suggests that probable clues include the fact that the CVC root stays constant across contexts (with some exceptions) whereas the affixes vary, that there are some linguistic contexts where the root occurs without any prefixes (relatively frequent in the input), and that the Tzeltal discourse convention of responding by repeating with appropriate deictic alternation (e.g., "I see it." "Oh, you see it.") highlights the root.

Abstract

In three experiments, the processing of lexical tone in Cantonese was examined. Cantonese listeners more often accepted a nonword as a word when the only difference between the nonword and the word was in tone, especially when the F0 onset difference between correct and erroneous tone was small. Same–different judgments by these listeners were also slower and less accurate when the only difference between two syllables was in tone, and this was true whether the F0 onset difference between the two tones was large or small. Listeners with no knowledge of Cantonese produced essentially the same same-different judgment pattern as that produced by the native listeners, suggesting that the results display the effects of simple perceptual processing rather than of linguistic knowledge. It is argued that the processing of lexical tone distinctions may be slowed, relative to the processing of segmental distinctions, and that, in speeded-response tasks, tone is thus more likely to be misprocessed than is segmental structure.

Abstract

Research on the exploitation of prosodic information in the recognition of spoken language is reviewed. The research falls into three main areas: the use of prosody in the recognition of spoken words, in which most attention has been paid to the question of whether the prosodic structure of a word plays a role in initial contact with stored lexical representations; the use of prosody in the computation of syntactic structure, in which the resolution of global and local ambiguities has formed the central focus; and the role of prosody in the processing of discourse structure, in which there has been a preponderance of work on the contribution of accentuation and deaccentuation to integration of concepts with an existing discourse model. The review reveals that in each area progress has been made towards new conceptions of prosody's role in processing, and in particular this has involved abandonment of previously held deterministic views of the relationship between prosodic structure and other aspects of linguistic structure

Abstract

Psycholinguists strive to construct a model of human language processing in general. But this does not imply that they should confine their research to universal aspects of linguistic structure, and avoid research on language-specific phenomena. First, even universal characteristics of language structure can only be accurately observed cross-linguistically. This point is illustrated here by research on the role of the syllable in spoken-word recognition, on the perceptual processing of vowels versus consonants, and on the contribution of phonetic assimilation phonemena to phoneme identification. In each case, it is only by looking at the pattern of effects across languages that it is possible to understand the general principle. Second, language-specific processing can certainly shed light on the universal model of language comprehension. This second point is illustrated by studies of the exploitation of vowel harmony in the lexical segmentation of Finnish, of the recognition of Dutch words with and without vowel epenthesis, and of the contribution of different kinds of lexical prosodic structure (tone, pitch accent, stress) to the initial activation of candidate words in lexical access. In each case, aspects of the universal processing model are revealed by analysis of these language-specific effects. In short, the study of spoken-language processing by human listeners requires cross-linguistic comparison.

Abstract

The human Xp11.23-p11.22 interval has been implicated in several inherited diseases including Wiskott-Aldrich syndrome; three forms of X-linked hypercalciuric nephrolithiaisis; and the eye disorders retinitis pigmentosa 2, congenital stationary night blindness, and Aland Island eye disease. In constructing YAC contigs spanning Xp11. 23-p11.22, we have previously shown that the region around the synaptophysin (SYP) gene is refractory to cloning in YACs, but highly stable in cosmids. Preliminary analysis of the latter suggested that this might reflect a high density of coding sequences and we therefore undertook the complete sequencing of a SYP-containing cosmid. Sequence data were extensively analyzed using computer programs such as CENSOR (to mask repeats), BLAST (for homology searches), and GRAIL and GENE-ID (to predict exons). This revealed the presence of 29 putative exons, organized into three genes, in addition to the 7 exons of the complete SYP coding region, all mapping within a 44-kb interval. Two genes are novel, one (CACNA1F) showing high homology to alpha1 subunits of calcium channels, the other (LMO6) encoding a product with significant similarity to LIM-domain proteins. RT-PCR and Northern blot studies confirmed that these loci are indeed transcribed. The third locus is the previously described, but not previously localized, A4 differentiation-dependent gene. Given that the intron-exon boundaries predicted by the analysis are consistent with previous information where available, we have been able to suggest the genomic organization of the novel genes with some confidence. The region has an elevated GC content (>53%), and we identified CpG islands associated with the 5' ends of SYP, A4, and LMO6. The order of loci was Xpter-A4-LMO6-SYP-CACNA1F-Xcen, with intergenic distances ranging from approximately 300 bp to approximately 5 kb. The density of transcribed sequences in this area (>80%) is comparable to that found in the highly gene-rich chromosomal band Xq28. Further studies may aid our understanding of the long-range organization surrounding such gene-enriched regions.

Abstract

This study tests the recent claim that Broca’s aphasics are impaired in automatic lexical access, including the retrieval of word meaning. Subjects are required to perform a lexical decision on visually presented prime target pairs. Half of the word targets are preceded by a related word, half by an unrelated word. Primes and targets are presented with a long stimulus-onset-asynchrony (SOA) of 1400 msec and with a short SOA of 300 msec. Normal priming effects are observed in Broca’s aphasics for both SOAs. This result is discussed in the context of the claim that Broca’s aphasics suffer from an impairment in the automatic access of lexical–semantic information. It is argued that none of the current priming studies provides evidence supporting this claim, since with short SOAs priming effects have been reliably obtained in Broca’s aphasics. The results are more compatible with the claim that in many Broca’s aphasics the functional locus of their comprehension deficit is at the level of postlexical integration processes.

Abstract

Stimulus-related changes in cerebral blood oxygenation were measured using high-resolution functional magnetic resonance imaging sequentially covering visual occipital areas in contiguous sections. During dynamic imaging, healthy subjects silently viewed pseudowords, single false fonts, or length-matched strings of the same false fonts. The paradigm consisted of a sixfold alternation of an activation and a control task. With pseudowords as activation vs single false fonts as control, responses were seen mainly in medial occipital cortex. These responses disappeared when pseudowords were alternated with false font strings as the control and reappeared when false font strings instead of pseudowords served as activation and were alternated with single false fonts. The string-length contrast alone, therefore, is sufficient to account for the activation pattern observed in medial visual cortex when word-like stimuli are contrasted with single characters.

Abstract

The aim of this paper is to discuss an inherent difficulty of PET (and fMRI) research in language production. On the one hand, language production presupposes some degree of freedom for the subject, on the other hand, interpretability of results presupposes restrictions of this freedom. This difficulty is reflected in the existing PET literature in some neglect of the general principle to design experiments in such a way that the results do not allow for alternative interpretations. It is argued that by narrowing down the scope of experiments a gain in interpretability can be achieved.

Abstract

[Seven one-page psycholinguistic sketches]

Abstract

Nobel's legacy, or the metamorphosis of what is idealistic Ever since the first Nobel prize in literature was awarded to Prudhomme in 1901, the decisions of the Swedish Academy have been subject to criticism. What is surprising in the changing decision policy as well as in its criticism is the fact that Alfred Nobel's original intentions are hardly ever taken into account: the Nobel prize is a philanthropic prize, it is not meant to select and honour the most eminent literary work but the work with maximal benefit to human beings. What is even more surprising is the fact that no one seems to care that the donator's Last Will is regularly broken.

Abstract

In this article, we discuss the implications of the fact that adult second language learners (outside the classroom) universally develop a well-structured, efficient and simple form of language–the Basic Variety (BV). Three questions are asked as to (1) the structural properties of the BV, (2) the status of these properties and (3) why some structural properties of ‘fully fledged’ languages are more complex. First, we characterize the BV in four respects: its lexical repertoire, the principles according to which utterances are structured, and temporality and spatiality expressed. The organizational principles proposed are small in number, and interact. We analyse this interaction, describing how the BV is put to use in various complex verbal tasks, in order to establish both what its communicative potentialities are, and also those discourse contexts where the constraints come into conflict and where the variety breaks down. This latter phenomenon provides a partial answer to the third question,concerning the relative complexity of ‘fully fledged’ languages–they have devices to deal with such cases. As for the second question, it is argued firstly that the empirically established continuity of the adult acquisition process precludes any assignment of the BV to a mode of linguistic expression (e.g., ‘protolanguage’) distinct from that of ‘fully fledged’ languages and, moreover, that the organizational constraints of the BV belong to the core attributes of the human language capacity, whereas a number of complexifications not attested in the BV are less central properties of this capacity. Finally, it is shown that the notion of feature strength, as used in recent versions of Generative Grammar, allows a straightforward characterization of the BV as a special case of an I-language, in the sense of this theory. Under this perspective, the acquisition of an Ilanguage beyond the BV can essentially be described as a change in feature strength.

Abstract

Words can be distinguished by segmental differences or by suprasegmental differences or both. Studies from English suggest that suprasegmentals play little role in human spoken-word recognition; English stress, however, is nearly always unambiguously coded in segmental structure (vowel quality); this relationship is less close in Dutch. The present study directly compared the effects of segmental and suprasegmental mispronunciation on word recognition in Dutch. There was a strong effect of suprasegmental mispronunciation, suggesting that Dutch listeners do exploit suprasegmental information in word recognition. Previous findings indicating the effects of mis-stressing for Dutch differ with stress position were replicated only when segmental change was involved, suggesting that this is an effect of segmental rather than suprasegmental processing.

Abstract

This article explores the relation between language and cognition by examining the case of "absolute" (cardinal direction) spatial description in the Australian aboriginal language Guugu Yimithirr. This kind of spatial description is incongruent with the "relative" (e.g., left/right/front/back) spatial description familiar in European languages. Building on Haviland's 1993 analysis of Guugu Yimithirr directionals in speech and gesture, a series of informal experiments were developed. It is shown that Guugu Yimithirr speakers predominantly code for nonverbal memory in "absolute" concepts congruent with their language, while a comparative sample of Dutch speakers do so in "relative" concepts. Much anecdotal evidence also supports this. The conclusion is that Whorfian effects may in fact be demonstrable in the spatial domain.

Abstract

We propose that the choice between the auxiliaries hebben 'have' and zijn 'be' in Dutch is determined by a particular semantic feature of verbs. In particular we propose a feature of meaning [IEPS] for 'inferable eventual position or state' that characterizes whether the action denoted by the verb allows us to determine the eventual position or state of the verb's highest argument. It is argued that only verbs which exhibit the feature [+IEPS] or which obtain the feature compositionally in the syntax select zijn as their auxiliary. Our analysis is then compared to a number of other analyses of auxiliary selection in Dutch.

Abstract

Mutations of the renal-specific chloride channel (CLCN5) gene, which is located on chromosome Xp11.22, are associated with hypercalciuric nephrolithiasis (kidney stones) in the Northern European and Japanese populations. CLCN5 encodes a 746 amino acid channel (CLC-5) that has approximately 12 transmembrane domains, and heterologous expression of wild-type CLC-5 in Xenopus oocytes has yielded outwardly rectifying chloride currents that were markedly reduced or abolished by these mutations. In order to assess further the structural and functional relationships of this recently cloned chloride channel, additional CLCN5 mutations have been identified in five unrelated families with this disorder. Three of these mutations were missense (G57V, G512R and E527D), one was a nonsense (R648Stop) and one was an insertion (30:H insertion). In addition, two of the mutations (30:H insertion and E527D) were demonstrated to be de novo, and the G57V and E527D mutations were identified in families of Afro-American and Indian origin, respectively. The G57V and 30:H insertion mutations represent the first CLCN5 mutations to be identified in the N-terminus region, and the R648Stop mutation, which has been observed previously in an unrelated family, suggests that this codon may be particularly prone to mutations. Heterologous expression of the mutations resulted in a marked reduction or abolition of the chloride currents, thereby establishing their functional importance. These results help to elucidate further the structure-function relationships of this renal chloride channel.