Domperidone at a dose of 4 mg/kg significantly raised circulating prolactin levels in male and female rats although this increase was .apprx. 4-fold higher in females compared with males. No effect on LH [luteinizing hormone] secretion was observed. The LH and prolactin responses to GnRH [gonadoliberin] and TRH, respectively, were investigated with isolated perfused pituitary glands obtained from domperidone-pretreated animals. For females, the basal release of prolactin was raised by domperidone pretreatment and the responsiveness of the pituitary to GnRH was markedly attenuated. When domperidone was added to the perfusing media, high concentrations (100 .mu.g/ml) reduced both the basal and TRH-stimulated prolactin secretion from pituitaries of untreated male and female rats; however, lower doses (1 .mu.g/ml and 10 ng/ml) were ineffective in altering prolactin release. The pituitary LH responses to GnRH were similarly reduced by the presence of 100 .mu.g domperidone/ml in the medium.