OBJECTIVE Blood activation during extracorporeal circulation is associated with morbidity and mortality in cardiac surgery. This activation can be diminished by usage of heparin-coated circuits. Nitric oxide has also been reported to influence humoral and cellular components of blood. This study was performed to determine biomaterial-dependent part of blood activation. METHODS Fresh, whole human blood mixed with Ringer's solution was circulated through a heart-lung machine for two and half hours. Five circuits were heparin-coated (group HC), whilst five other circuits were uncoated (group NC). During the last half hour NO was added to the oxygen/air mixture. METHODS Blood activation was estimated by measuring following parameters: interluekin 6, complement activation products C3a and terminal complement complex, and oxygen free radicals (OFR) production capacity, which was determined using chemiluminescence enhanced by serum opsonized zymosan (SOZ) and phorbol myristate acetate (PMA). Granulocyte activation was measured as release of myeloperoxidase (MPO) and human neutrophil lipocalin (HNL). RESULTS OFR in granulocyte suspension stimulated by SOZ and PMA were significantly lower in the NC group, mostly later during ECC. Similarly, lower neutrophil and monocyte counts were observed in this group. NO increased superoxide production in the whole blood in heparin-coated circuits, but did not change OFR in isolated granulocytes. MPO was also affected by heparin-coating. NO supply seemed to increase release of MPO and HNL. It is concluded that heparin-coating contributed to reduction of biomaterial-dependent blood activation. An addition of NO at late stage of ECC tended to influence this activation.