To estimate the influence of blood-flow on complement generation and the relation with dialysis efficacy (KT/V) 10 patients underwent cuprophan hemodialyses for 6 h using low (200 ml/min) or high (400 ml/min) blood-flow (n = 40). Dialysis with high blood-flow compared to low induced a more rapid drop in leukocyte count and a more pronounced leukocyte rebound. Net generation of C3a (microgram/min) was also larger at all 15 measuring points during high blood-flow dialysis and there was significantly larger total generation of C3a (after 3 h p < 0.05, after 6 h p < 0.05) as compared to low blood-flow. Reaching a KT/V of 1.2-1.4 with high blood-flow induced a 40% larger total net generation of C3a and 21% more of TCC than with low blood-flow. Net generation of TCC (AU/min) was higher during the first and last parts of high blood-flow dialysis compared to low. In conclusion, increased blood-flow in order to increase dialysis efficiency (KT/V 1.2-1.4) results in larger net infusion of complement products with possible impact on immune response and complement-associated pathophysiological mechanisms.