We examined the effects of acute hemorrhagic pancreatitis in the sheep lung lymph fistula preparation. Pulmonary lymph flow and transvascular protein clearance increased after pancreatitis was induced by injection of sodium taurocholate and trypsin into the pancreas in control sheep. However, neither parameter was altered in sheep pretreated with the protease inhibitor, Trasylol (initial bolus injection, 5,000 KIU/kg followed by 5,000 KIU/kg for 4 h). In addition, in the control animals, both peripheral granulocyte count and the arterial fibrinogen concentration decreased, but these changes did not occur after pancreatitis in the Trasylol-pretreated animals, suggesting that the generation of proteases is responsible for granulocyte sequestration and intravascular coagulation after pancreatitis. The platelet count decreased comparably in both groups, indicating a lack of involvement of platelets in lung vascular injury. Therefore, generation of proteases is an important factor in the mediation of increased lung vascular permeability after acute hemorrhagic pancreatitis.