The serum IL-6 and TNF alpha response to cardiopulmonary bypass surgery was studied in 12 patients. Human neutrophil elastase was also measured in order to detect the presence of neutrophil activation. Peripheral venous blood samples were obtained before, during, and 1, 2, 3 and 6 days after surgery. Intra-operative samples were also obtained from the coronary sinus and pulmonary artery. Cardiopulmonary bypass stimulated the immediate release of IL-6 into the coronary, pulmonary and systemic circulations. TNF alpha was transiently detected in the pulmonary circulation in seven patients. Surgery also induced early and sustained activation of neutrophils, which peaked 24 h following maximum IL-6 release. Both IL-6 and TNF alpha not only enhance neutrophil activation, but also stimulate an adhesive neutrophil-cardiac myocyte interaction which is associated with the release of toxic oxygen radicals. Their detection, in association with concomitant neutrophil activation, suggests a possible pathway for enhanced neutrophil mediated myocardial damage following cardiopulmonary bypass surgery.