The protective action of protease inhibitors (Trasylol, IP-315) the synthetic antifibrinolytic agent (EACA) and heparin in the prevention of acute pancreatic necrosis was evaluated on the basis of serum amylase, histological examination and survival of dogs. Heparin was found to be the most efficient agentin protecting dogs from pancreatic necrosis, the other protease inhibitors were much less effective.In dogs pretreated with heparin no elevation of fibrinogen level and no inhibition of fibrinolysis were observed. These changes were markedly expressed in control dogs with pancreatic necrosis and those receiving profease inhibitors. The total proteolytic activity of pancreas homogenates was investigated. A significant difference in the heparin-treated dogs in comparison with the controls was observed. Similar differences were obtained on testing acid phosphatase in both groups. Successful prevention of acute pancreatitis by heparin can also be explained as being due to the anti-clotting properties of this drug as well as to its action on the level of the pancreatic cell. It is also possible that heparin has a stabilizing effect on lysosomes, known to be the main source of hydrolases.