Infusion of 2 nmol atrial natriuretic factor (ANF) into the third cerebroventricle of conscious, orchidectomized male rats results in a significant inhibition of prolactin (PRL) secretion. This effect is prevented by prior treatment with the dopamine receptor antagonist, domperidone. Furthermore, domperidone reverses the inhibitory effect when given after ANF infusion. The PRL-inhibiting effect is absent as well following inhibition of tyrosine hydroxylase activity. These results suggest that ANF acts centrally at least in part via an interaction with endogenous dopaminergic systems and further suggests potent neuromodulatory actions of the peptide within the hypothalamus.