The elevation in serum prolactin (PRL) concentration in schizophrenic patients treated with typical antipsychotic drugs is well documented. Recently, increased prolactin levels have been reported in patients taking risperidone. The purpose of this study was to explore the effect of the atypical antipsychotic drug risperidone on serum prolactin, and to investigate the relationship between the change in PRL and the therapeutic outcome. In this study, 30 male inpatients with a diagnosis of chronic schizophrenia (DSM-III-R) were assigned to 12 weeks of treatment with risperidone after a 2-week washout period. The risperidone dose was fixed at 6 mg/day. Clinical efficacy was determined using the Positive and Negative Syndrome Scale (PANSS). Serum PRL was assayed in serum by radioimmunometric assay in schizophrenic patients before and after 12-week treatment, as compared to 30 age-matched normal male subjects. The results showed that risperidone treatment significantly increased the serum PRL. A significant and positive relationship between the change in PRL at pre- and post-treatment and the reduction rate of PANSS positive subscore was observed. Risperidone treatment significantly increased the serum PRL levels of schizophrenic patients. There was a close relationship between the improvement in positive symptoms and the change of serum PRL level before and after risperidone treatment. The serum PRL levels at baseline could be used to predict the responses of schizophrenic patients to risperidone.