We measured plasma levels of interleukin-6 and C-reactive protein at the orifice of the left coronary artery and at the great cardiac vein in patients who had coronary artery disease and those who had angiographically normal coronary arteries (controls). We also measured coronary microvascular resistance in the control group. We found increased levels of interleukin-6 in the coronary circulation of patients who had coronary artery disease compared with controls. This increase correlated with C-reactive protein production in the coronary circulation and coronary microvascular resistance. These findings suggest that a localized cytokine/inflammatory pathway functions in the coronary circulation and that interleukin-6 is involved in modulating coronary vascular tone.