The coronary flow reserve is abnormal in syndrome X, but the response to the cold pressor test, which in normals produces flow-mediated endothelium-dependent epicardial coronary dilation, has not been studied. In this study, in 12 patients with typical syndrome X and angiographically normal coronary arteries, the response to the cold pressor test was abnormal with a mean fall in diameter (10 +/- 8%) in 6 patients, no change in 1, and a minimal increase (4 +/- 2%) in 5 patients (normal increase 12 +/- 1%). The coronary blood flow fell slightly during the cold pressor test, and the coronary vascular resistance increased significantly (from 2.4 +/- 1.1 to 3.2 +/- 1.7 mm Hg/cm.s-1.mm2; p = 0.05), both abnormal responses. This study confirms that in syndrome X patients there is coronary endothelial dysfunction which is apparent in response to physiological stimuli induced by the cold pressor test.