Endotoxin (lipopolysaccharide) concentrations were determined in the systemic venous blood in nine patients undergoing cardiopulmonary bypass. Lipopolysaccharide concentrations were low and stable until institution of cardiopulmonary bypass (preanesthetic concentration 0.128 +/- 0.032 ng/ml [mean +/- standard error of the mean]; prebypass level 0.136 +/- 0.03 ng/ml). After the start of bypass, the plasma concentration of lipopolysaccharide rose progressively with time to a mean value of 0.347 +/- 0.044 ng/ml (p less than 0.01), which was 0.227 ng/ml above baseline. Upon release of the aortic clamp, an additional rise in lipopolysaccharide concentration occurred after to 5 to 15 minutes to a mean value of 0.428 +/- 0.06 ng/ml (p less than 0.001) above baseline. The concentration then decayed to the baseline level 45 to 75 minutes after termination of bypass. The peak lipopolysaccharide concentration above the baseline positively correlated with both the length of bypass (r = 0.839, p less than 0.005) and the duration of aortic cross-clamping (y = 0.0030X + 0.173 r = 0.85, p less than 0.001) when flow was nonpulsatile. The peak occurred during the period of myocardial and pulmonary reperfusion. This rise in endotoxin concentration may be one of the factors responsible for the prolonged postoperative recovery seen in some patients.