The histamine H2-receptor antagonist cimetidine, which has recently been introduced for the treatment of gastric and duodenal ulcers and haemorrhage, respectively, stimulates prolactin (PRL) secretion. The release of PRL after a bolus injection of the compound is significantly higher in female than in male volunteers, and is more pronounced during the luteal than during the follicular phase of the menstrual cycle. Oral administration of the drug stimulates PRL to a similar extent as parenteral administration. Treatment of male and female volunteers with cimetidine for 20 days (1 g/day orally) resulted in elevated serum PRL concentrations in both sexes. Basal LH levels as well as the response to 25 microgram LH-RH were not significantly changed after treatment. Testosterone levels in males and oestradiol levels in females were not altered. Luteal progesterone, however, was significantly diminished in the menstrual cycles when cimetidine was given. The mechanism underlying the stimulatory effect of cimetidine on PRL secretion is not clear, but it does not seem that this ability is exerted via an inhibition of pituitary dopamine receptors. The dopaminergic effect of lisuride, an ergot alkaloid, could not be reversed by cimetidine.