Adrenomedullin is a potent vasodilatory peptide originally identified in human pheochromocytoma. Plasma adrenomedullin increases during and after cardiopulmonary bypass (CPB). However, the site at which production of adrenomedullin is augmented has not been identified. In the present study, we examined the contribution of the cerebral vasculature to the production of adrenomedullin in patients before, during, and after CPB. Ten patients undergoing coronary artery bypass grafting with mild hypothermic CPB were studied. Cerebral blood flow was measured using the Kety-Schmidt method before, during, and after CPB. Plasma adrenomedullin concentrations from radial artery and internal jugular bulb blood were measured by radioimmunoassay, and cerebral adrenomedullin production was evaluated. Adrenomedullin production in the cerebral vasculature was significantly enhanced after CPB and correlated with aortic cross-clamping time. The cerebral adrenomedullin production may contribute to the increased plasma level of adrenomedullin after CPB. CONCLUSIONS Plasma adrenomedullin has been reported to increase in humans after cardiac surgery involving cardiopulmonary bypass. In this study, we demonstrated that cerebral adrenomedullin production may contribute to the increased plasma level of adrenomedullin after cardiopulmonary bypass.