Cardiopulmonary bypass generates a systemic inflammatory response, including the activation of leukocytes, contributing to postoperative morbidity. To evaluate whether the use of heparin-treated extracorporeal circuits could reduce the inflammatory reaction in patients undergoing cardiopulmonary bypass, we conducted a prospective clinical study on 14 patients having coronary artery bypass in whom perfusion was done randomly with either Duraflo II heparin-treated circuits or with nontreated circuits. In both groups systemic heparinization was performed before cardiopulmonary bypass. The use of heparin-treated circuits resulted in a reduction of systemic inflammatory activation during cardiopulmonary bypass. This was reflected by lower plasma levels of soluble tumor necrosis factor receptors (p < 0.05) and of interleukin-6 and interleukin-8 (p < 0.05), manifest after release of the aortic crossclamp. Furthermore, 6 and 12 hours after aortic crossclamp release significantly lower levels of the soluble E-selectin (p < 0.05) were observed in the Duraflo II group. In patients in whom noncoated circuits were used, a significant decrease in circulating soluble intercellular adhesion molecule 1 (p < 0.05) was found early during bypass. All these observations suggest that the use of a heparin-treated extracorporeal circuit reduces the systemic inflammatory activation and may after the leukocyte-endothelium interaction.