Domperidone at a dose of 4 mg/kg significantly raised circulating prolactin levels in male and female rats although this increase was approximately 4-fold higher in females compared with males. No effect on LH secretion was observed. This LH and prolactin responses to Gn-RH 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 Gn-RH was markedly attenuated. When domperidone was added to the perfusing media, high concentrations (100 microgram/ml) reduced both the basal and TRH-stimulated prolactin secretion from pituitaries of untreated male and female rats although lower doses (1 microgram/ml and 10 ng/ml) were ineffective in altering prolactin release. The pituitary LH responses to Gn-RH were similarly reduced by the presence of 100 microgram domperidone/ml in the medium.