Background: The use of warm blood cardioplegia is usually associated with that of warm cardiopulmonary bypass (CPB). Little is known, however, about the effect of temperature during bypass on neutrophil-endothelium interactions, which are currently considered a key component of the inflammatory response to CPB. Methods and Results: Twenty-five patients operated on under CPB were studied. Core temperature during bypass was kept normothermic (33.5°C to 37°C) in 14 and lowered to 28°C to 30°C in the 11 remaining patients. The two groups were otherwise comparable. Arterial blood samples were collected before CPB and 30 minutes, 4 hours, and 24 hours thereafter. Samples were assayed for interleukin-1 receptor antagonist (IL- 1ra), soluble intercellular adhesion molecule 1 (sICAM-1), and elastase, which are markers of cytokine production, cytokine-upregulated endothelial ligands for neutrophil adhesion molecules, and degranulation secondary to adhesion of neutrophils to endothelial cells, respectively. IL-1ra levels (mean±SEM) peaked 4 hours after bypass and were significantly higher in the warm group (87 926±24 067 versus 18 090±5798 mg/L, P<.02). Peak values of sICAM-1, which occurred 24 hours after bypass, were correspondingly higher in warm patients (414±74 versus 298±23 μg/L in cold patients). In keeping with these data, warm patients released significantly more elastase at both the 30-minute (703±101 versus 349±55 μg/L, P<.01) and 4-hour (627±116 versus 324±31 μg/L, P<.03) post-CPB study points. Conclusions: Temperature profoundly affects neutrophil-endothelium interactions, which leads one to question the use of systemic normothermia in patients at higher risk of suffering from postbypass inflammation-mediated organ damage.