This study was designed to test whether indomethacin given in drinking water attenuates the severity of the acute hemorrhagic pancreatitis induced in mice fed a choline-deficient ethionine diet (CDE), and improves their survival. Three doses of indomethacin were tested, 20, 10 and 5 mg of indomethacin/l of drinking water, and their effects on the histopathology of the pancreas and liver, serum amylase activity levels, and mortality were determined. Even though 20 and 10 mg/l suppressed pancreatic injury, and the accompanying shock-like state, the mice died due to indomethacin hepatotoxicity. Hepatotoxicity was minimal at a dose of 5 mg/l, which resulted in preservation of significant amounts of normal pancreatic parenchyma, subsequent regeneration of acinar cells, and an increased survival of the mice. The results suggest that prostaglandins may play an important role in the pathogenesis of acute hemorrhagic pancreatitis, and that indomethacin attenuates the severity of the induced disease.