To investigate whether the release of endotoxin during cardiopulmonary bypass (CPB) is determined by perfusion-related factors, endotoxin concentrations were determined before, during, and after CPB in 21 male patients (age range 45-75 years) undergoing elective coronary artery bypass grafting. Hemodynamic parameters and oncotic pressure were also measured. Significant increases in endotoxin concentrations were observed after the start of CPB (P < 0.005), before aortic cross-clamp release (P < 0.05), and after aortic cross-clamp release (P < 0.05). The median endotoxin concentration after cessation of CPB was 0.264 EU/ml (range < 0.036-0.480 EU/ml). Endotoxin concentrations derived from the prime solutions were not contributory. Positive correlations were found between arterial pressure after the start of CPB and the endotoxin concentration 10 min after (r = 0.58, P < 0.01) and between the duration of aortic cross-clamping and the endotoxin concentration after the cessation of CPB (r = 0.64, P < 0.005). Arterial pressure after the start of CPB, the duration of aortic cross-clamping, and decrease in oncotic pressure appeared to be independent variables in a forward variable selection model that predicted endotoxin concentrations after CPB. We conclude that in patients undergoing elective coronary artery bypass grafting, an early phase of endotoxin release during CPB could be demonstrated, and that this is due to vasoconstriction. The endotoxin concentrations after the cessation of CPB were determined by early vasoconstriction, duration of aortic cross-clamping, and hypo-oncotic hemodilution.