Gene-targeting in mice is a powerful tool to define molecular mechanisms of ischemic heart disease that determine infarct size, postinfarct left ventricular (LV) remodeling, and arrhythmogenesis. Coronary ligation in mice is becoming a widely used model of myocardial infarction (MI), but the pathophysiologic consequences of MI in mice and its relevance to human MI have not been fully elucidated. To characterize structural and functional changes during evolving MI, we analyzed 2-dimensional-based reconstruction of the left ventricle by noninvasive echocardiography obtained 1 day and 1 week after surgical ligation of the left anterior descending coronary artery in mice. Sequential 2-dimensional short-axis cineloops of the left ventricle were used to measure LV mass, and LV volumes at end-diastole and end-systole. Echocardiographic infarct size was estimated by measuring the volume of akinetic LV segments. Histologic infarct size was measured by planimetry of 9 transverse sections of each heart. There was close correlation between the 2 methods (31% ± 20% of LV mass and 34% ± 17% of LV area, respectively; y = .83x + 7.9, r = 0.96, P < .01). LV volumes at end diastole increased significantly between 1 day and 1 week (51 ± 17 μL vs 78 ± 46 μL, respectively, P < .05). The relative change in LV volumes at end diastole varied as a function of infarct size (r = 0.93, P < .01). LV mass and the extent of hypertrophy of noninfarcted segments also varied with infarct size (r = 0.92, P < .01; r = 0.90, P < .01, respectively). Thus, echocardiography is an accurate noninvasive tool for determination of infarct size and quantitative characterization of postinfarct remodeling in the mouse model of MI. Alterations in cardiac structure and function after coronary ligation in mice closely resemble pathophysiologic changes in human ischemic heart disease. (J Am Soc Echocardiogr 2002;15:601-9.)