Coagulation proteins are known to affect the complement system and neutrophils. To assess the influence of thrombosis on complement and neutrophils during hemodialysis, whole human blood obtained from normal donors and anticoagulated with either 0.8 or 2.0 U/mL of heparin was recirculated for 4 h through cellulose acetate hollow fibers in vitro. Plasma fibrinopeptide A (FPA) levels were measured to assess thrombosis, whereas the activation of the complement system was evaluated at various stages by determining plasma C3a(desArg), C5a(desArg), and SC5b-9 concentrations. The activation of circulating neutrophils was assessed by quantitation of the extracellular release of the intragranular proteins elastase and lactoferrin. Thrombosis was observed when 0.8 U/mL of heparin was used, as indicated by a 36-fold increase in (FPA) levels at 240 min of recirculation and occasional grossly visible blood clots. In contrast, no increase in FPA or clot formation was observed with 2.0 U/mL of heparin. The higher dose of heparin was also associated with a lesser increase in plasma C3a(desArg) and C5a(desArg) concentrations, an observation that is compatible with either an inhibitory effect of heparin or a stimulatory effect of coagulation on the complement system. Plasma elastase or lactoferrin concentrations increased during hemodialysis but were not dependent on heparin dosage at any time. It was concluded that anticoagulation with higher heparin concentration inhibits complement activation in the hemodialysis circuit, but it does not affect neutrophil degranulation.