Pancreatic necrosis is now recognized as a principal determinant of survival in acute pancreatitis. However, it is currently unknown how frequently pancreatic necrosis develops in acute pancreatitis, how often pancreatic necrosis becomes secondarily infected, and whether sterile pancreatic necrosis represents an indication for surgery or can be treated by conservative means. In 194 patients with unequivocal acute pancreatitis, pancreatic necrosis developed in 38 (20%), as documented by dynamic pancreatography, and was confirmed by histologic diagnosis at surgery in 28. All patients were prospectively treated by medical means. Patients with pancreatic necrosis who remained persistently febrile underwent fine needle aspiration for bacterial culture. Infected pancreatic necrosis was demonstrated in 27 of the 38 patients (71%) with pancreatic necrosis and was treated by open drainage, yielding a mortality rate of 15%. All 11 patients with demonstrated sterile pancreatic necrosis, including 6 with pulmonary and renal insufficiency, were successfully treated without surgery. Pancreatic necrosis occurs in approximately 20% of patients with acute pancreatitis and is necessary for the development of secondary pancreatic infection. However, pancreatic necrosis by itself, even when accompanied by organ failure, is not an absolute indication for surgery. A trial of medical treatment for all patients with sterile pancreatic necrosis is in order.