Prolonged veno arterial extracorporeal bypass (50-80% of cardiac output) was evaluated in normal, unanesthetized sheep. The evaluation protocol included serial measurements of hemodynamics, pulmonary and renal function, serum enzymes to detect organ damage, and detailed studies of coagulation and platelets. Blood exposure surfaces were primarily polyvinyl chloride and silicone rubber. Gas interfaces were carefully excluded with the exception of four experiments utilizing bubble oxygenators. Heparin dose was titrated to maintain activated clotting to two to three times baseline. Characteristics of 48 hour uncomplicated extracorporeal circulation in 8 sheep included normal hemodynamics, mild respiratory alkolosis negligable hemolysis, slight gradual increase in heart, liver, and muscle enzymes. The most significant changes occurred in coagulation and platelets characterized by an initial reduction in coagulation factors with a continued reduction in platelet count and return to normal clotting factors during extracorporeal circulation. This is followed by a two times normal increase in platelets and fibrinogen following extracorporeal circulation.