BACKGROUND Regional left ventricular (LV) dysfunction may occur in patients with coronary artery disease (CAD) in the absence of infarction, but the causes of this phenomenon are unclear. We sought to identify whether changes in regional LV function were related to stenosis severity, using sensitive new ultrasound markers of function. METHODS We studied 67 individuals with no history of infarction and with normal LV systolic function: 49 patients with CAD and 18 control subjects without CAD. All patients underwent color Doppler tissue imaging, integrated backscatter (IB), anatomic M-mode echocardiography, and strain rate imaging to detect changes in structure and function. Peak early and late diastolic myocardial velocity, cyclic variation of IB, wall thickness, and percent wall thickening were measured in each basal and mid segment. Strain rate and peak systolic strain were calculated in each wall. CAD was defined as >or=50% diameter stenosis. Normokinetic segments (n = 354) subtended by CAD were divided according to stenosis severity into 3 groups: group 1 (subtended by 50%-69% stenosis); group 2 (subtended by 70%-98% stenosis); and group 3 (subtended by >or=99% stenosis). Each parameter in each group was compared with that in 216 segments from control subjects. RESULTS Segments subtended by significant CAD showed lower peak early and late diastolic myocardial velocity compared with control segments. Group 3 showed significantly lower myocardial velocities than group 2 for both peak early (4.8 +/- 1.8 vs 6.0 +/- 2.0 cm/s, P <.05) and late (4.5 +/- 2.1 vs 5.6 +/- 2.1 cm/s, P <.05) diastolic myocardial velocity. Group 3 also showed a significantly lower cyclic variation IB than did control segments (6.7 +/- 2.3 vs 7.9 +/- 2.6 dB, P <.05), but there was no difference in calibrated IB, wall thickness, strain parameters, or percent wall thickening. These differences were not attributable to the distribution of segments for patients with severe CAD, nor were they explained on the basis of collaterals. CONCLUSION Although the absolute values show overlap between groups, the results of this study indicate that subtle changes of regional LV function may occur in the absence of infarction, in association with severe coronary stenoses.