Serum prolactin concentrations increased approximately 6-fold after oral or intravenous administration of 10 mg of metoclopramide to adult men. Prolactin remained significantly elevated up to 9 h after oral metoclopramide and for at least 2 h after iv metoclopramide. Bethanechol did not increase serum prolactin, and atropine did not inhibit metoclopramide-induced prolactin elevation, suggesting that the cholinergic-like properties of metoclopramide were not responsible for the observed prolactin responses. Pre-treatment with 500 mg L-dopa inhibited the early metoclopramide-induced prolactin increase, which is consistent with the possibility that metoclopramide acts by inhibiting dopamine-mediated hypothalamic secretion of prolactin inhibitory factor. As a potent stimulus of prolactin release, metoclopramide may be useful in clinical investigation of hypothalamic-pituitary function.