Objective: The hypothesis that clozapine reduces serious physically and verbally aggressive behavior of persons with schizophrenia whose symptoms did not respond to typical neuroleptic treatment was tested. Method: Incident reports of aggression and restraint of 75 such inpatients were reviewed for 3 months before clozapine treatment and for 6 months of clozapine treatment. BPRS scores were also examined. Twenty-eight patients with no incidents were removed from study. Results: There were significantly fewer incidents of physical aggression per month per patient on clozapine than before clozapine (mean +/- S.D. = 0.13 +/- 0.25 vs. 0.54 +/- 0.93; t = 3.4, df = 46, p<0.002) and a similar decline in verbal aggression (0.21 +/- 0.31 vs. 0.73 +/- 0.83; t = 4.3, df = 46, p<0.000). On clozapine, 49% (n = 23) of patients had fewer incidents of physical aggression, 36% (n = 17) showed no change and 15% (n = 7) showed more. Seventy percent (n = 33) of patients had fewer incidents of verbal aggression, 4% (n = 2) showed no change and 25% (n = 12) had more. During the 3 months before clozapine, 14 patients (30%) were restrained a total of 40 times. During the first 6 months of clozapine treatment, three patients (6%) were restrained a total of six times. There were significant decreases in BPRS hostility, positive, negative and psychosis scores. Conclusion: Clozapine appears to reduce serious aggression among some patients.