We investigated digestive enzyme release following a short-term pancreatic duct obstruction in rats. An in vivo experiment demonstrated that a 6-hour pancreatic duct obstruction reduced digestive enzyme release evoked both by endogenously released cholecystokinin (CCK) due to pancreaticobiliary diversion and by exogenous administration of CCK8. In vitro experiments also showed that pancreatic duct obstruction reduced the maximal CCK8-evoked amylase secretion. Amylase secretion evoked by the calcium ionophore A23187 and by phorbol myristate acetate was also markedly decreased. These data suggest that pancreatic duct obstruction probably interferes with the secretory process downstream of hormone receptor binding, intracellular Ca2+ release and protein kinase C activation.