The effects of intracerebroventricular (i.c.v.) administration of pituitary adenylate cyclase activating polypeptide38 (PACAP38) on prolactin (PRL) secretion and the activity of tyrosine hydroxylase (TH) were examined in adult male and lactating rats with or without suckling stimulus. In adult male rats and lactating rats with suckling stimulus, administration of PACAP38 (0.25 or 1 nmol) decreased PRL secretion and increased the activity of TH in the stalk-median eminence. On the other hand, the injection of PACAP38 did not affect PRL secretion and TH activity in lactating rats without sucking stimulus. Administration of PACAP6-38 (4 nmol), a specific receptor antagonist, also had no effect on PRL secretion and TH activity in adult male rats. These results suggest that i.c.v. administration of PACAP inhibits PRL secretion mediated by dopamine neuron within the hypothalamus, but the effects of PACAP differ depending on the physiological condition of animals. These observed effects of PACAP on PRL release may be pharmacological responses rather than physiological responses.