There is no method to objectively evaluate left ventricular (LV) function from contrast-enhanced images. We tested the feasibility of evaluating regional LV function by using power modulation imaging. In protocol 1, 9 anesthetized closed-chest pigs were studied. Images were obtained during contrast infusion at baseline, during LAD occlusion and reperfusion. In protocol 2, images were obtained in 20 patients (14 wall-motion abnormalities; 6 controls) during contrast enhancement. Off-line, frame-by-frame, semiautomated endocardial border detection was followed by color encoding of endocardial motion, followed by segmentation and calculation of regional fractional area changes. In all animals, coronary occlusions resulted in hypokinesis and decreased fractional area changes in LAD-related segments only, which were reversed during reperfusion. In patients, wall-motion analysis was in agreement with an expert reader of dynamic images in 92.5% segments, with interobserver variability of 12.5%. Color encoding of endocardial motion from contrast-enhanced power modulation images allows accurate quantitative assessment of regional LV function.