The effects of pituitary adenylate cyclase activating polypeptide (PACAP) on regional blood flow in the eye and other tissues were investigated in albino rabbits. Direct determination of the flow from a cannulated vortex vein, in animals pretreated with a vasopressin receptor antagonist, showed that i.v. infusion of either PACAP-27 or PACAP-38 caused a dose-dependent (0.08-0.64 pmol/kg per min) decrease in the uveal vascular resistance. Regional blood flow was determined, with radioactive microspheres, during i.v. infusion of PACAP-27 or PACAP-38 (0.64 pmol/kg per min) in rabbits pretreated with hexamethonium and a vasopressin receptor antagonist. In these experiments, both PACAP-27 and PACAP-38 increased choroidal blood flow by about 50%, whereas there was no effect in the anterior uvea. Nor was there any major effect on blood flow in the anterior uvea after intracameral injection of PACAP-27 or PACAP-38 (3 pmol). The largest blood flow increases, caused by i.v. infusion of PACAP-27 or PACAP-38, were observed in the parotid gland, submandibular gland, eyelids and nictitating membrane. Local blood flow in the choroid plexus, pineal gland, posterior pituitary gland, stomach, kidney and adrenal gland was also significantly increased during the i.v. infusion of PACAP-27. The results of the present investigation indicate that PACAP-27 and PACAP-38 are about 100 times more potent than vasoactive intestinal polypeptide and peptide histidine isoleucine as vasodilators in the rabbit choroid and, possibly, also in many other tissues of the rabbit.