Role of the protease-antiprotease balance in peritoneal exudate during acute pancreatitis. The peritoneal exudate formed during experimental pancreatitis is toxic when administered intraperitoneally or intravenously to other animals. Overwhelming of the peritoneal antiprotease defences by proteolytic enzymes released from the pancreas may be a key factor responsible for this toxicity and is examined in the current study. Human pancreatitis exudates possessed tryptic amidase activity indicating trypsinogen activation. The trypsin inhibitory capacities of exudates were reduced indicating a degree of consumption of the peritoneal antiproteases. Of 21 exudates examined, three showed marked reduction of their trypsin inhibitory capacity indicating almost complete consumption of their antiproteases. All three patients were shocked at the time of sampling, two dying of fulminant pancreatitis within 24 h. Overwhelming of the peritoneal antiproteases was not confirmed, but may occur in a few instances where proteolytic enzyme release or zymogen activation continues. Intraperitoneal administration of exogenous antiproteases prolongs survival in rats with pancreatitis and has been suggested as a therapy in man. The current data suggests that few patients are likely to benefit from such an approach. 