OBJECTIVE: The long-term effects of a combination of clozapine and psychosocial treatment were evaluated in a sample of treatment- refractory state hospital patients with schizophrenia. METHODS: A repeated-measure design was used. Thirty-one patients with schizophrenia received both clozapine and an enhanced psychosocial treatment program. Data were collected at baseline and at one-year, two- year, and three-year follow-ups. Psychiatric symptoms, cognitive functioning, dyskinetic movements, and discharge rate were evaluated. RESULTS: Significant reductions in psychiatric symptoms and improvement in cognitive functioning were found. Differences in the pattern of reductions in positive and negative symptoms over the course of the study were noted. The majority of subjects improved sufficiently to be discharged. CONCLUSIONS: Clozapine, when combined with psychosocial treatment, is effective for treatment of patients with schizophrenia who are not responsive to other medications.