Bile exclusion from the gut exacerbates pancreatic duct obstruction-induced acute pancreatitis. We hypothesized that obstruction-induced acute pancreatitis involves an increase in circulating cholecystokinin (CCK), as bile and pancreatic juice exclusion from the gut stimulates duodenal CCK release. We studied 54 rats after the following operations: (1) sham operation (n = 18), (2) hepatic bile duct obstruction alone (n = 18), (3) hepatic bile duct and common bile-pancreatic duct obstruction (n = 18). Rats recovered and were killed in subgroups of six rats each at 3, 6, and 18 hr after operation; blood was collected for measurement of plasma CCK and amylase concentrations. Each pancreas was excised, weighed, and processed for histological examination; an acute pancreatitis score was determined. Combined bile and pancreatic duct obstruction induced acute pancreatitis and was associated with a marked increase of circulating CCK concentration. Bile duct obstruction alone did not induce acute pancreatitis but was associated with an increase of circulating CCK of lower magnitude. The time course of circulating CCK increase showed an early peak. These findings support our hypothesis and suggest that CCK plays a role in the pathogenesis of obstruction-induced acute pancreatitis.