Nitric oxide (NO), a unique biological mediator that has been implicated in many physiological and pathological processes, may have a significant influence on the course of acute pancreatitis. L-arginine administration partially protected the pancreas against caerulein-induced pancreatitis. By contrast, L-NNA administration enhanced the caerulein-induced degenerative alterations in the pancreatic acinar cells. Coadministration of L-arginine with L-NNA partly prevented the deleterious effects of L-NNA on rat pancreas. Thus, enhanced endogenous production of NO could confer protection against the development of hemorrhagic necrotizing pancreatitis.