Coronary disease or its risk factors has been reported to attenuate basal nitric oxide (NO) activity. Intravascular ultrasound was used in the present study to better understand this relation. Basal and stimulated NO activities were assessed in 53 stable subjects. Coronary diameter and velocity (0.014-inch Doppler wire) were measured at baseline and after intracoronary infusion of the NO synthase inhibitor N(G)-monomethyl-l-arginine, acetylcholine (10(-6) M), nitroglycerin (200 microg), and adenosine (24 microg). Intimal thickening was quantified with intravascular ultrasound. N(G)-monomethyl-l-arginine resulted in significant decreases in coronary blood flow (-14 +/- 48%), proximal coronary diameter (-10 +/- 18%), and distal coronary diameter (-10 +/- 9%, all p values <0.0001). Basal NO activity was unrelated to the presence of coronary disease as assessed by angiography and the burden of atherosclerosis as assessed by intravascular ultrasound. Conversely, stimulated NO activity correlated inversely with burden of coronary atherosclerosis (p <0.05). Basal NO activity is relatively preserved in patients who have moderate coronary disease and is not related to the degree of atherosclerosis as assessed by intravascular ultrasound. This is in contradistinction to the impairment of stimulated NO activity in the coronary circulation that characterizes atherosclerosis.