Acute pancreatitis, in most cases, is a self-limiting disease with few complications and a low mortality. By contrast, the severe form of the illness frequently leads to multiple organ failure which may prove fatal. Death usually is thought to result from autodigestion of the pancreas by prematurely activated enzymes and damage to distant organs by pancreatic enzymes spilled into the circulation. The key role in this process is attributed to trypsin, the trigger of the pancreatic enzyme cascade. Although examination of pancreatic tissue during pancreatitis suggests cellular damage by digestive enzymes, there are several observations that rob this hypothesis of some of its plausibility and invite reassessment of the role of pancreatic enzymes, and in particular trypsin, in the pathogenesis of acute pancreatitis.(1) Active trypsin is rarely found in more than trace amounts in the pancreas of patients or experimental animals that died of the disease [1-4].(2) The integrity of the pancreas is protected from the potentially lethal effect of its enzymes by a multiplicity of safeguards:(a) Potentially dangerous enzymes are present as inactive zymogens sequestered in zymogen granules.(b) The zymogen granule is an actively acidified compartment precluding trypsin activity or zymogen activation [5].(c) The Ca-concentration (< 1 mM) of pancreatic secretions favors degradation of trypsinogen rather than activation.(d) Pancreatic secretions contain a specific trypsin inhibitor, capable of inactivating up to 20% of potential trypsin activity.