The prolactin response to an antipsychotic drug, bromperidol was studied in 24 schizophrenic in-patients (13 males, 11 females). Eight patients were given 6 mg/day, 8 were given 12 mg/day and 8 were given 18 mg/day. Duration of treatment was 3 weeks. Plasma concentrations of bromperidol and reduced bromperidol were measured by high-performance liquid chromatography, and that of prolactin was measured by radioimmunoassay. Bromperidol treatment significantly(P<0.01) increased plasma concentration of prolactin each week. The mean±S.D. of the Δ-prolactin (the mean concentration during treatment minus the pretreatment concentration) was 13.3±12.4 ng/ml. Multiple regression analysis showed that the Δ-prolactin concentration was significantly greater in females than in males (P<0.05) and correlated to plasma concentrations of bromperidol (P<0.001) and reduced bromperidol (P<0.0001). These results suggest that the prolactin response to bromperidol treatment depend on plasma concentrations of both bromperidol and reduced bromperidol and gender, and that reduced bromperidol is involved in the pharmacological effects during bromperidol treatment.