In the present study we evaluate the possibility that xanthine oxidase released by damaged pancreas could act as a source of oxidative damage in systemic tissues during the early stages of acute pancreatitis. This was accomplished by evaluating the effects of xanthine oxidase inhibition with oxypurinol infused into the portal vein. Under these conditions, we inhibited the enzyme before it reached the liver and other distant organs, without inducing changes in the severity of pancreatic damage. Results indicate that pancreatitis parallels increases in xanthine oxidase activity in plasma. Superoxide radicals generated by this enzyme appears to be involved in the decrease of reduced glutathione levels in the plasma and liver. In addition, xanthine oxidase inhibition prevents the infiltration of neutrophils into the lungs. We conclude that oxygen free radicals generated by xanthine and xanthine oxidase released to the bloodstream are involved in the systemic organ failure associated with acute pancreatitis.