In an effort to elucidate factors that determine the severity of an attack of acute pancreatitis, we have quantitated the extent of necrosis and of apoptosis in five different models of experimental acute pancreatitis. Severe pancreatitis was induced by obstructing the opossum common bile-pancreatic duct, by administering to mice 12 hourly injections of a supramaximally stimulating dose of caerulein, and by feeding young female mice a choline-deficient, ethionine-supplemented diet. In each of these models of severe pancreatitis, marked necrosis but very little apoptosis was found. Mild pancreatitis was induced by obstructing the rat common bile-pancreatic duct and by infusing rats with a supramaximally stimulating dose of caerulein. In contrast to our findings in severe pancreatitis, mild pancreatitis was characterized by very little necrosis but a high degree of apoptosis. Our finding that the severity of acute pancreatitis is inversely related to the degree of apoptosis suggests that apoptosis may be a teleologically beneficial response to acinar cell injury in general and especially in acute pancreatitis.