OBJECTIVE: The purpose of this study was to find predictive criteria for response to clozapine. METHOD: Single photon emission computed tomography studies of cerebral perfusion were done in 24 treatment- resistant schizophrenic patients while they were taking typical neuroleptics and again after they had been treated with clozapine for 6 months. Perfusion ratios of the subjects categorized as responders or nonresponders to clozapine and of the subjects in the two treatment conditions were compared. The ratios with significant between-group differences were compared to those from a normal database. RESULTS: Before clozapine, while taking neuroleptics, subjects who became responders to clozapine showed higher thalamic, left basal ganglia, and right prefrontal perfusion. Nonresponders to clozapine had lower prefrontal perfusion and responders had higher subcortical perfusion than subjects in the normal database. The subcortical perfusion of the responders decreased when they received clozapine. CONCLUSIONS: The study of cerebral perfusion may contribute to the prediction of response to clozapine.