In a randomized, double-blind clinical study in 29 patients undergoing elective coronary artery surgery, we assessed the role of ketanserin, an inhibitor of serotonin-induced vasoconstriction and weak α1 sympathetic blocker, in reducing endotoxaemia and postoperative hypermetabolism. Male patients without major organ dysfunction were allocated randomly to receive either ketanserin or placebo. Hypermetabolism was defined as an increase in oxygen consumption in the early postoperative hours (ΔV̇(O2)). Circulating endotoxin (P = 0.04) and postoperative ΔV̇(O2) (P = 0.03) were lower in the ketanserin patients. Endotoxaemia was associated also with low vascular filling. From these preliminary results we conclude that treatment with ketanserin during cardiac surgery may reduce but not abolish endotoxaemia and postoperative hypermetabolism.