The physiological regulation of PRL secretion seems to involve the central serotonin system, since plasma PRL levels are enhanced by serotoninergic agonists and serotonin re-uptake blockers. The aim of this study was to evaluate whether the influence of oestrogens on PRL is mediated by the hypothalamic serotonin system. The PRL response to fenfluramine, a serotonin agonist that releases the amine and inhibits its re-uptake, was assessed in 10 normal men (aged 18-25 years) and in six castrated men (aged 18-24 years). In both groups, the effect of fenfluramine on PRL secretion was also evaluated on the sixth day after receiving clomiphene citrate, an oestrogen antagonist and partial agonist. In castrated men, fenfluramine administration was also performed on the seventh day after the last dose of testosterone enanthate (200 mg i.m. every 3 weeks for 4 months). Our results demonstrate that in normal men fenfluramine treatment significantly enhances plasma PRL levels, and clomiphene citrate treatment significantly reduces this effect. In castrated men, fenfluramine is also able to enhance PRL secretion but to a lesser extent; after clomiphene citrate treatment the increase of plasma PRL levels induced by fenfluramine rises to the normal range. We therefore suggest that in man oestrogens and aromatizable androgens influence PRL secretion at least in part by involving the activation of the hypothalamic serotonin system.