OBJECTIVE: This study examined the combined effectiveness of clozapine and a comprehensive inpatient psychosocial rehabilitation program on the clinical functioning and aggressive behaviors of patients with chronic schizophrenia. METHODS: Two groups of 11 subjects each were selected from among patients being treated in the social learning program at Fulton (Mo.) State Hospital. Group 1 subjects were placed on clozapine at various times after the introduction of the program, while group 2 subjects remained on traditional antipsychotics throughout the study period. Group 1 and group 2 subjects were matched on clinical functioning as measured by the Time-Sample Behavioral Checklist (TSBC). For each subject, scores on six TSBC subscales were examined at five time points. Data were analyzed using repeated-measures multiple analysis of variance and univariate analyses of variance. Data on frequency of aggressive behaviors were aggregated into three six-month time periods and were analyzed using Wilcoxon signed-rank tests. RESULTS: Both groups demonstrated significant improvement on several measures. However, the addition of clozapine resulted in accelerated improvement for group 1 subjects, especially in aggressive behaviors. CONCLUSIONS: Comprehensive psychosocial treatment programming resulted in significant improvements in clinical functioning for many inpatients. Clozapine may enhance responsiveness to such programming for some patients.