The effects of intraventricular infusions of ovine prolactin (oPrl) on both endogenous prolactin levels in serum, and upon the release of prolactin and cortisol in response to treatment with either TRH, 5-HTP or morphine were studied in rhesus monkeys. A single injection of oPrl (10.8 micrograms) into the lateral ventricles of castrated males resulted in CSF levels of around 350 ng/ml 60 min later, but no oPrl could be detected in the blood. Endogenous (rhesus) prolactin levels in serum fell during this time to about half their initial values in oPrl-treated animals but not in the bovine serum albumin (BSA)-injected controls. Ovine prolactin was infused continuously into either the lateral or third ventricles of ovariectomized, estrogen-treated females for 6 days from an osmotic minipump (2.7 micrograms/h). CSF levels of oPrl were about 250 ng/ml though none was found in the serum. The release of endogenous prolactin by TRH (1 microgram) was greatly reduced compared with BSA-treated controls. 5-HTP (2.5 mg/kg together with carbidopa pretreatment) also stimulated much less prolactin release in females chronically infused with oPrl and there was some evidence for a similar effect in males following a single intraventricular injection. CSF levels of 5-HTP itself, and of 5-HIAA and HVA were similar throughout this experiment in both oPrl and BSA-infused animals. Finally, prolactin released by morphine (5 mg) was highly attenuated in females receiving oPrl intraventricularly. In contrast to those on serum prolactin, the effects of these various treatments on serum cortisol were unaltered by intraventricular oPrl. These results suggest that the primate brain contains a neural system which is directly responsive to prolactin, and which can modulate this hormone's release under either basal conditions or following treatment with substances that stimulate its release by acting either directly on the pituitary or upon the neural systems regulating pituitary function. These results are compatible with the presence of increased dopamine in the portal blood, though this was not measured in these experiments.