The effects of cholecystokinin receptor antagonist CR 1392 was studied in a model of mild acute pancreatitis induced in rats by four subcutaneous injections of the secretagogue caerulein. A single subcutaneous injection of 50 mg/kg body weight of CR 1392 caused a dramatic reduction in serum amylase concentration and pancreatic wet weight as well as histologic improvement of the caerulein-induced acute pancreatitis when given 30 min before the first caerulein injection. CR 1392 was also effective in reducing the elevated serum amylase activity, pancreatic weight, and histologic alterations even when administered after the pancreatitis had been induced. These present observations suggest that CR 1392 remains active for more than 3 h and blocks the action of caerulein on the pancreas.