This study was performed to evaluate the accuracy of intravascular ultrasound for the assessment of coronary artery vasomotion and endothelial function in patients with atherosclerosis. Twenty patients with luminal irregularities on the coronary angiogram and a high cholesterol level (287 +/- 19 mg/dl) (group 1) and six patients with angiographically smooth arteries and a minimally elevated cholesterol level (197 +/- 12 mg/dl) (group 2) were studied. A mechanical intravascular ultrasound probe (4.3F) was placed into the proximal segment of the coronary artery. The ultrasound images were recorded on super VHS videotape and were then digitized allowing the measurement of the lumen area and then the calculation of a mean intimal thickness index. Endothelial function was studied during sympathetic stimulation by a cold pressor test and, after increasing coronary blood flow, by intracoronary papaverine administration; a 1 mg bolus of linsidomine was then administered into the coronary artery. Patients in group 1 had a higher mean intimal thickness (1.52 +/- 0.64 mm) than those in group 2 (0.18 +/- 0.08 mm) (p < 0.001). In response to sympathetic stimulation, a vasoconstricting effect occurred in group 1 (9.5 +/- 1.3 mm2 vs 11.4 +/- 1.2 mm2 at baseline, p < 0.05), while a vasodilating action was observed in the control group (11.6 +/- 2.1 mm2 vs 10.4 +/- 1.8 mm2 at baseline, p < 0.05). After papaverine infusion, a trend toward a vasoconstricting effect was observed in response to increased flow in group 1 (10 +/- 1.3 mm2 vs 11.4 +/- 1.2 mm2 at baseline, p < 0.05). that was not observed in group 2 (9.4 +/- 2 mm2 vs 8.9 +/- 1.9 mm2, p = NS). Linsidomine infusion induced a significant vasodilating effect in both groups (p < 0.001). In conclusion, intravascular ultrasound may be considered a useful tool to assess endothelial function of large coronary arteries and to obtain the precise relationship between wall thickness and the vasomotor response.