PACAP (1-27) (the N-terminal fragment of PACAP-38) is a novel neuropeptides originally isolated from bovine hypothalamus, also found in humans and rats. PACAP (1-27) shows considerable homology with Vasoactive Intestinal Polypeptide (VIP), and can stimulate adenylate cyclase much more potently than VIP. The PACAP(1-27)-induced increase in pancreatic venous blood flow was blocked by PACAP(6-27) but not by atropine. Therefore, the endocrine secretagogue effect of PACAP(1-27) is primarily mediated by the PAC(1) receptor, and that PACAP(1-27) may interact with muscarinic receptor function in PACAP-induced insulin and glucagon secretion in the canine pancreas in vivo.