Routinely used iodinated contrast media have complex vasomotor effects on several arterial districts. All classes of iodinated radiographic contrast media are vasoactive, with iso-osmolar dimers inducing the smallest changes in vascular tone. The mechanisms responsible for contrast-induced vasomotor changes are not fully elucidated and are likely to be multifactorial. Although contrast-induced vasomotility is usually considered as an unwanted "side effect", recent findings suggest that it might indeed be useful in exploring the functional integrity of the vessel wall. We found that atherosclerosis has an impact on the type of the contrast-induced coronary vasomotor reaction. In fact, angiographically normal coronary segments show divergent vasomotor reactions to iodixanol or iopromide according to the presence/absence of, and distance from, a coronary atherosclerotic lesion located in their proximity. The mechanism responsible for this vasomotor effect does not apparently involve flow-mediated vasodilatation or endothelial nitric oxide synthesis. On the other hand, a cyclooxygenase product may be, at least in part, responsible for the vasodilating effect of non-ionic agents on epicardial coronary arteries, since contrast-induced vasodilatation is strongly inhibited in the presence of indomethacin. These findings have potential clinical implications, since the analysis of contrast-induced coronary vasomotion might result in a new test capable of evaluating vascular functional integrity. Such a test might be alternative or complementary to the tests based on muscarinic agonists (acetylcholine) or serotonin, which are known to evaluate the nitric oxide pathway.