Myocardial Depressant Factor (MDF) is a small peptide circulating in the blood of all mammalian species tested in a variety of shock states including endotoxic, hemorrhagic, cardiogenic, bowel ischemic, acute pancreatitis, burn, and traumatic shock. MDF is produced by the action of proteolytic enzymes released by the ischemic pancreas. MDF acts to depress myocardial contractility, constrict the splanchnic arteries and impair reticuloendothelial system phagocytosis. Several pharmacologic agents prevent the formation of MDF including membrane stabilizers (e.g., glucocorticoids), protease inhibitors (e.g., aprotinin), converting enzyme inhibitors (e.g., captopril), prostaglandins (e.g., PGE1 and PGI2), thromboxane synthetase inhibitors (e.g., imidazole, PTA2) and local anesthetics (e.g., lidocaine). Prevention of MDF formation or action improves survival. Thus, MDF is an important mediator of shock pathophysiology and should be considered in the therapy of circulatory shock states.