Pancreatic juice from four patients with acute pancreatitis was collected at 4° C from uncomplicated fistulae or by catheterization of the pancreatic duct. The concentration of free trypsin, chymotrypsin, and elastase, as well as the corresponding zymogens in the specimens, was estimated. With the exception of the juice from one patient with a fistula, who secreted zymogens and free chymotrypsin only during the first two postoperative days, all specimens contained free enzymes exclusively, including those specimens obtained by catheter during the period of observation. The apparent lack of pancreatic trypsin inhibitor in the secretions of our patients, and earlier reports of low levels or absence of this inhibitor after abdominal operations, may reflect a prerequisite in the development of acute pancreatitis. In this scheme, the trigger mechanism in the premature activation of pancreatic zymogens may be provided by autoactivation of trypsinogen or its activation by enzymes of the blood-clotting or fibrinolytic systems. Some evidence in support of this hypothesis is presented.