Background.: Heparin bonding of the cardiopulmonary bypass (CPB) pump circuit decreases complement activation and fibrinolysis. It is not known whether inflammatory cytokines produced during CPB can also be modulated by the more biocompatible heparin-coated circuit. Methods.: This initial study evaluated the impact of heparin-bonded CPB circuits on production of the cytokines interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-a), IL-6, and IL-8 in adults undergoing complex cardiac operations with prolonged CPB. Twenty patients had blood samples drawn immediately before and at hourly intervals after the start of CPB using either a conventional oxygenator and circuit (n = 14) or a covalently bonded heparin oxygenator and circuit (n = 6). Levels of IL-1, TNF-a, IL-6, and IL-8 were measured in all serum samples using a "sandwich" enzyme-linked immunosorbent assay. Results.: The levels of IL-6 and IL-8 increased in a time-dependent fashion in both groups, but the response was significantly less over time in the heparin-bonded group (p < 0.05) for both IL-6 and IL-8. Levels of IL-1 and TNF-a were not significantly elevated with lengthening bypass interval in either group. Conclusions.: These data indicate that the use of heparin-coated bypass pump circuits results in lower serum levels of the inflammatory cytokines IL-6 and IL-8 than standard circuits. Biocompatible materials that decrease the inflammatory response to CPB may ultimately reduce the morbidity associated with cardiac operations.