Purpose: Cardiopulmonary bypass (CPB) induces a complex inflammatory response characterized by complement, neutrophil, and platelet activation. To investigate the effects of an anti-factor D monoclonal antibody (Mab 166–32) on inhibition of the alternative complement cascade, we undertook the following study, using human blood in a simulated pediatric CPB circuit. Methods: We performed 5 paired experiments on Mab 166–32 and an irrelevant control Mab at 18 μg/ml of human blood. The extracorporeal circuit was primed with 250 ml of human blood and 100 ml of lactated Ringer's solution. During CPB, the hematocrit was maintained at 26–28%, and pump flow remained constant at 500 ml/min. After initiation of CPB, the blood temperature was reduced to 27°C, where it was maintained for 70 minutes, followed by 10 minutes of rewarming and 30 minutes of normothermic CPB. Extracorporeal circulation lasted for 120 minutes, and blood was sampled at 0, 5, 10, 25, 40, 55, 70, 80, and 120 minutes. Activation of complement, neutrophils, and platelets was assessed with immunofluorocytometry and ELISA. Results: After 120 minutes of CPB, the results (mean ± standard error) were as follows:TableConclusions: Complement activation via the alternative complement pathway induces the inflammatory responses in CPB, which are effectively inhibited by the anti-factor D Mab 166–32.