Heparin coating modifies complement activation during extracorporeal circulation much more effcclively than systemically administered heparin. This rabbit study was undertaken to address possible mechanisms responsible for this difference. We evaluated the effect of heparin coating on complement activation and subsequently the release of leukocyte inflammatory mediators during extracorporeal circulation through a simplified circuit. We found in the heparin-coated group a significantly reduced complement hemolytic activity (CH5,)), remaining higher leukocyte numbers, significantly decreased release of P-glucuronidase, and most strikingly a complete pre-