Serum prolactin levels were monitored for 2 hours after injection of chlorpromazine (CPZ) 50 mg intramuscularly (i.m.) in 6 male normal controls and 14 newly admitted male chronic schizophrenics. The increase in serum prolactin levels in the male normal controls was not significantly different from that in patients. Serum prolactin levels were compared in 18 male and 22 female psychotic patients of various psychiatric diagnoses who received 50 mg of CPZ i.m., and 7 male and 6 female patients who received 25 mg CPZ i.m. No significant sex or dose differences were seen in the magnitude of the prolactin response after i.m. CPZ. These results suggest that doses of CPZ 25 or 50 mg i.m. may result in maximal prolactin secretion in most subjects and that lower doses are needed to test the hypothesis that dopamine receptors are supersensitive in schizophrenia or the affective psychoses. In six patients with mixed diagnoses, serum levels of CPZ and other active metabolites were determined by radioreceptor binding assay; peak serum drug levels were highly correlated with peak serum prolactin levels (4 = 0.92) during the first 2 hours following CPZ 50 mg i.m.