The authors compared efficacy and safety of risperidone and clozapine for the treatment of psychosis in a double-blind trial with 10 subjects with Parkinson's disease (PD) and psychosis. Mean improvement in the Brief Psychiatric Rating Scale psychosis score was similar in the clozapine and the risperidone groups (P=0.23). Although the mean motor Unified Parkinson's Disease Rating Scale score worsened in the risperidone group and improved in the clozapine group, this difference did not reach statistical significance. One subject on clozapine developed neutropenia. In subjects with PD, risperidone may be considered as an alternative to clozapine because it is as effective for the treatment of psychoses without the hematologic, antimuscarinic, and seizure side effects. However, risperidone may worsen extrapyramidal symptoms more than clozapine and therefore must be used with caution.