Intracisternal administration of synthetic human β-endorphin increases plasma prolactin concentration, and this effect is blocked by naloxone. Drugs which stimulate dopamine receptors (apomorphine or bromocriptine) or increase availability of dopamine (pargyline) inhibited the effect of β-endorphin on plasma prolactin. Drugs which antagonize dopamine receptors (haloperidol) or decrease availability of dopamine (α-methyltyrosine) potentiated the effect of β-endor-phin on plasma prolactin. Some of these drugs act only in neurons and not in anterior pituitary, supporting a brain site of action for these drug interactions with β-endorphin which altered prolactin secretion. These pharmacological studies provide support for a concept of dopaminergic mediation of β-endorphin-induced prolactin secr