The biocompatibility of the Terumo (Terumo Corporation, Tokyo, Japan) covalent heparin coating method in a cardiopulmonary bypass (CPB) circuit was evaluated in ex vivo and in vivo experiments. In the ex vivo experiment, fresh human heparinized blood primed both a miniature heparin coated circuit (HCC) and the identical noncoated circuit (NCC), and was circulated simultaneously for 2 hr (n = 6). In the in vivo experiment, 10 rabbits underwent 2 hr of CPB under systemic heparinization (ACT > 400 sec) with HCC (n = 5) and with NCC (n = 5). In the ex vivo study, thrombin/anti-thrombin III complex, thromboglobulin, platelet factor IV, granulocyte elastase, and C3a were significantly lower in the HCC than in the NCC at 60 and 120 min of circulation (p < 0.05). In the in vivo study, platelet counts (percent of value at 10 min of CPB) were significantly higher in the HCC than NCC (HCC:NCC 87 +/- 10:71 +/- 12 at 60 min, 81 +/- 17:56 +/- 16 at 120 min). Scanning electron microscopic examination of the circuits showed less significant adhesion and pseudopod formation of platelets in the HCC than NCC in both ex vivo and in vivo situations. These results demonstrate that this heparin coated CPB circuit provides superior biocompatibility compared with a noncoated circuit by reducing the activation of the coagulation cascade, platelets, leukocytes, and complement.