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The effect of sulpiride, a neuroleptic agent, on the secretion of prolactin by the anterior pituitary gland of the rat was studied. A significant increase in serum prolactin was observed after subcutaneous administration of the drug. Although sulpiride (0·10µmol/l or 0·14 mmol/l) had no effect on the secretion of newly synthesized or radioimmunoassayable prolactin in vitro, the drug significantly overcame the inhibitory action that dopamine (0·50 µmol/l) exerted on prolactin secretion. Rats implanted with a prolactin-secreting pituitary tumour MtTW15 showed an inhibition of prolactin biosynthesis and release. Injection of these rats with sulpiride restored prolactin biosynthesis and release of the hormone toward normal levels. These results demonstrate that sulpiride has a direct effect on the pituitary antagonizing the inhibitory effects exerted by dopaminergic mechanisms, although the drug itself does not stimulate the secretion of prolactin in vitro. Sulpiride may have a direct action on the pituitary lactotrophs in vivo, but effects at higher centres have not been excluded.