Pituitary adenylate cyclase activating polypeptide 38 (PACAP 38), a novel peptide of the vasoactive intestinal polypeptide (VIP) family, was shown to stimulate enzyme secretion in the dispersed rat pancreatic acini. The dose-response of pancreatic enzyme secretion to PACAP 38 was nearly identical with that to VIP. In the presence of a submaximal dose of PACAP 38 (1 nM), amylase release stimulated by an agonist working via the elevation of intracellular cyclic AMP (VIP, dibutyryl cAMP) was additionally responded, but the amylase release stimulated by an agonist via the elevation of cytosolic free calcium (carbachol, cholecystokinin) was potentiated synergistically. The present data suggest that PACAP 38 is a new candidate for the cAMP-mediated stimulant of pancreatic exocrine secretion.