Cardiopulmonary bypass (CPB) involves extensive contact between blood and synthetic surfaces and may result in blood cell activation and plasma protein alterations. This study determines the effect of Duraflo II heparin treated CPB circuits (Bentley Laboratories, Irvine, CA) on calves under simulated clinical conditions. Calves were placed on CPB for 4 hr, and activated clotting times were maintained above 480 sec with systemic heparin. Better preserved platelet number and function, lower fibrinopeptide A levels, and lack of thrombus deposition were observed in the Duraflo II treated group, relative to the untreated control group, during the entire bypass period. The results suggest that despite high doses of circulating heparin in calves during CPB, the use of extracorporeal circuits with improved blood compatibility still provides measurable benefit.