The effect of pituitary adenylate cyclase-activating polypeptide (PACAP) on arginine vasopressin (AVP) release was investigated in conscious rats. Intracerebroventricular (i.c.v.) administration of PACAP raised the plasma AVP concentration in a dose-dependent manner (50-500 pmol/rat), and the maximum effect was obtained at 5 min after the administration. This AVP-releasing effect was not due to a fall of blood pressure, increase of plasma Na or decrease of plasma volume, all of which are known to stimulate AVP release. PACAP had little effect on blood pressure at a low dose, but at higher doses increased it. Vasoactive intestinal peptide (VIP), which is homologous to PACAP, also raised the plasma AVP concentration by i.c.v. injection. An antagonist for VIP receptor, [Lys, Pro, Arg, Tyr]-VIP inhibited the VIP-induced increase of plasma AVP, but had little effect on PACAP-induced increase of plasma AVP. These results suggest that PACAP stimulates AVP release, via specific receptors which are distinct from VIP receptors.