It has been reported that cimetidine, an H2-receptor antagonist, stimulates PRL secretion in postpartum. In the present study, the PRL response to two H1-receptor antagonists, promethazine and d-chlorpheniramine, was studied in 38 normal puerperal women on day 1 after delivery. Serum PRL levels decreased significantly after a single dose of promethazine (100 mg) given im (5 women) or d-chlorpheniramine (20 mg) given iv (6 women). In contrast, no significant change in PRL levels was observed after only saline infusion (6 women). Promethazine, given concomitantly to an iv bolus injection of TRH (200 micrograms) (6 women) and d-chlorpheniramine, given at the onset of suckling (6 women), did not alter stimulation of PRL release induced by these challenges. These results suggest the involvement of histamine H1 receptors in the regulation of basal PRL secretion in postpartum and would indicate that they do not participate in the mechanisms underlying suckling-induced PRL release.