Fifteen DSM-III-R diagnosed schizophrenics characterized by long-term neuroleptic nonresponse and significant negative symptoms were evaluated with the Positive and Negative Syndrome Scale, a well-operationalized measure of psychopathology, on a baseline neuroleptic and weekly thereafter across 26 weeks of clozapine treatment in order to explore clozapine's effect on other domains of schizophrenic psychopathology beyond its effect on positive symptoms. Mean differences from baseline indicated significant improvement on positive, negative, cognitive, excitement, and depression subscales after 12 weeks. Improvement observed after 12 weeks of clozapine treatment reliably predicted scores observed at week 26. There were no further significant improvements on any symptom profile, including positive and negative symptoms, in this long-term, nonresponder group between weeks 12 and 26. Overall, clozapine proved to affect a broad spectrum of discrete and nonoverlapping domains of psychopathology in this schizophrenic sample.