OBJECTIVE This study was conducted to evaluate to what extent the cardiopulmonary bypass (CPB) procedure in patients undergoing coronary artery bypass grafting (CABG) contributes to the systemic inflammatory response. Therefore, we measured bactericidal permeability increasing protein (BPI) as an indicator of neutrophil activation, interleukin 6 as inducer of the acute phase response, and lipopolysaccharide binding protein and C-reactive protein as parameters of the acute phase response in patients undergoing CABG either with or without the use of CPB. METHODS Prospective study. METHODS Cardiopulmonary surgery department in a university hospital. METHODS Sixteen patients undergoing elective CABG were included. Eight patients underwent surgery with CPB, and eight patients underwent surgery without CPB (non-CPB). METHODS In the CPB group, blood samples were taken upon induction of anesthesia, at the start of aortic cross-clamping, at aortic unclamping, and 0.5, 4, 8, and 18 h thereafter. In the non-CPB group, blood samples were taken upon induction of anesthesia, and 0.5, 4, 8, and 18 h after completion of the bypass graft anastomoses. RESULTS BPI release from neutrophil granules markedly increased during surgery in CPB patients but not in non-CPB patients. The increase in acute phase reactants, however, was the same in both patient groups. CONCLUSIONS These data indicate that the acute phase response in CABG patients, which has historically been ascribed to the CPB procedure, is predominantly caused by the surgical procedure per se. Early neutrophil activation, however, is seen only when extracorporeal circulation is used.