Since prolactin secretion is under vigorous dopaminergic inhibition, neuroleptic drugs can, because of their capacity to block dopamine receptors, produce large increases in plasma prolactin levels in man and laboratory animals. The capacity of intramuscular (i.m.) chlorpromazine and 6 of its metabolites to increase plasma prolactin levels in male rats was compared. 7-Hydroxychlorpromazine produced increases in plasma prolactin equivalent to those produced by chlorpromazine. The following metabolites had no effect on plasma prolactin levels after i.m. injections of 5 mg/kg: 8-hydroxychlorpromazine; 7,8-dihydroxychlorpromazine; 8-hydroxy-7-methoxychlorpromazine; 7-methoxychlorpromazine; and chlorpromazine sulfoxide. 8-Hydroxychlorpromazine, 7-methoxychlorpromazine, 7,8-dihydroxychlorpromazine and chlorpromazine sulfoxide had no effect even after 25 mg/kg i.m. The capacity to increase rat plasma prolactin correlates highly with other methods of determining potential antipsychotic activity of chlorpromazine and its derivatives.