Islet amyloid polypeptide (IAPP), a novel peptide recently isolated from the amyloid substance of pancreatic islets, has been localized in normal islet B cell granules, suggesting its physiological action in exocrine pancreatic function. In the present study, the direct effect of IAPP on secretagogue-stimulated pancreatic enzyme secretion was investigated using dispersed rat pancreatic acini. Various concentrations of IAPP (10(-5) -10(-10) M) showed no significant influence on amylase release stimulated either by submaximal doses of CCK-8 (10(-11) M), secretin (0.5 x 10(-6) M) or carbachol (10(-6) M), or by a maximal dose of vasoactive intestinal peptide (10(-8) M). These results may provide negative evidence for a physiological significance of IAPP in rat pancreatic enzyme secretion.