In order to elucidate the relationship between plasma dehydroepiandrosterone (DHA) and sulpiride-induced hyperprolactinemia (of 60 day duration) in normal men, five normal men (aged 27-46) were administered daily 300 mg of sulpiride orally for 60 days to induce hyperprolactinemia. Plasma levels of prolactin, DHA and cortisol were measured by radioimmunoassay before sulpiride treatment, at day 14 and day 60 after initiation of the treatment. Plasma levels of prolactin after the administration rose significantly (P less than 0.001) to 71.6-95.3 ng/ml in four out of the five subjects compared with those of the controls. In the same four subjects the mean DHA values in plasma were elevated significantly (P less than 0.05) to 877 +/- 160 ng/dl from the mean baseline values (669 +/- 91 ng/dl). The elevated values remained during sulpiride treatment. Plasma levels of cortisol did not change significantly during sulpiride administration in all subjects. Our results suggest that sulpiride-induced hyperprolactinemia sustained at least 14-60 days in normal men stimulates the adrenal cortex to secrete DHA.