Beta-thromboglobulin (beta TG), serotonin (5HT) and fibrinopeptide A (FPA) were assessed in twenty-two normal donors before, during, and at the end of leukapheresis. Seven procedures were carried out adding heparin to the circuit, and seven adding acetyl salicylic acid (ASA). The remaining eight procedures were carried out using only citrate and served as controls. Plasma beta TG increased both during and after the apheresis, together with a significant decrease of the intra-platelet content. Platelet 5HT did not show significant changes whereas FPA increased significantly. Using heparin, we obtained a complete prevention of FPA cleavage during the entire procedure, while beta TG increased at the middle of the procedure. No significant effects were observed using ASA both on beta TG and FPA levels. These features clearly indicate the activation of platelets and the thrombin generation in the apheresis circuit. Nevertheless, the activation of the clotting system seems to be predominant, as supported by the improved effect of heparin on beta TG and FPA amounts.