In this event-related brain potential (ERP) study, we examined how semantic and referential aspects of anaphoric noun phrase resolution interact during discourse comprehension. We used a full factorial design that crossed referential ambiguity with semantic incoherence. Ambiguous anaphors elicited a sustained negative shift (Nref effect), and incoherent anaphors elicited an N400 effect. Simultaneously ambiguous and incoherent anaphors elicited an ERP pattern resembling that of the incoherent anaphors. These results suggest that semantic incoherence can preclude readers from engaging in anaphoric inferencing. Furthermore, approximately half of our participants unexpectedly showed common late positive effects to the three types of problematic anaphors. We relate the latter finding to recent accounts of what the P600 might reflect, and to the role of individual differences therein.