The lining of blood vessels releases a variety of substances that cause relaxation of the smooth muscle and one of these important endothelium- derived relaxing factors is believed to be nitric oxide. Although the role of nitric oxide in the coronary circulation of animals is known, its role in intact human coronary circulation is not understood. This study was designed to examine the role of nitric oxide in controlling coronary artery tone. This was studied by means of using a blocker of nitric oxide production, L-NMMA. L-NMMA produced 16% reduction in the size of the large coronary arteries and up to 36% increase in the tone of the small blood vessels. In the presence of risk factors that can cause arteriosclerosis (hardening of the arteries), the availability of nitric oxide from coronary blood vessels was reduced substantially. Our findings imply that patients with risk factors may have increased coronary blood vessel tone due to reduced nitric oxide activity, and because of the reduced release of nitric oxide during stress, dilation of blood vessels may be limited during stress, and therefore contribute to ischemia. It may also contribute to increased risk of clotting and thus of heart attack, and to more rapid progression of coronary atherosclerosis.