The regulation of flow and diameter of the coronary arteries depends on many factors. In normal subjects, increased coronary flow is associated with an increase in diameter of the epicardial coronary vessels. The coupling of these two independent variables depends on the integrity of endothelial function. In isolated arteries suppression of the endothelium induces an abnormal vasomotor response to acetylcholine. The presence of atherosclerotic lesions on the coronary vessels also induces the opposite response to the administration of acetylcholine, even in apparently normal segments. Other physiological coronary vasodilator stimuli, especially those which increase the concentration of noradrenaline, become vasoconstrictor in diseased coronary vessels. Finally, increasing coronary blood flow is not associated with increases in coronary diameter in patients with coronary atherosclerosis. This loss of flow-dependent vasodilatation is an early and diffuse phenomenon in subjects with cardiovascular risk factors. The authors have shown that this inversion of vasomotor responses observed by angiographic techniques, may also be documented by endocoronary ultrasonography. Their results demonstrate that the vasodilatation induced by papaverine or by the cold pressor test in 6 normal subjects is lost in 20 patients with coronary atherosclerosis and that the administration of Sin 1 induces a comparable vasodilatation in normal and diseased vessels. This study confirms that endothelial function is globally altered in atherosclerotic coronary artery disease.