Three methods for assessment of fractional area change (FAC) and conventional versus cross-sectional segmentation were compared under conditions known to occur frequently during stress echocardiography. Quantitative analysis of 80 echocardiograms obtained from healthy subjects, patients with left ventricular (LV) dysfunction and after coronary artery bypass grafting included segmental and cross-sectional FACs by the centroid method with fixed and floating reference and a method with floating external reference. All segmental and cross-sectional FACs were equally sensitive to LV dysfunction, and segmental FACs failed to accurately predict the location of coronary lesions. The centroid method with floating reference and cross-sectional FACs were the least affected by surgery induced intrathoracic heart motion. In moderate to severe LV dysfunction FAC by the centroid method with floating reference and cross sections were rarely within normal limits. Cross-sectional FACs may prove to be useful in stress echocardiography. For viability studies segmental FAC by fixed reference appears to be the method of choice.