A multi-center double-blind trial was performed on 48 patients with severe acute pancreatitis. All patients were treated with intraperitoneal lavage. One group (n = 22) was also treated with high doses of the protease inhibitor, aprotinin (Trasylol; Bayer AG, Leverkusen, Germany) administered intraperitoneally. Eight patients died, giving a total mortality of 16.6%. No difference was observed between the two groups. Altogether, 12 patients were operated on, corresponding to 25%. In the group not treated with aprotinin, 6 patients were operated on because of pancreatic necrosis, compared with none in the treated group. The difference was statistically significant. There were no significant differences between the two groups with regard to organ failure or other complications. It was concluded that aprotinin counteracts the development of pancreatic necrosis when given intraperitoneally in high doses to patients with severe acute pancreatitis, thus reducing the need for surgical intervention in these patients.