Genetically altered mice are useful to understand cardiac physiology. Myocardial contrast echocardiography (MCE) assesses myocardial perfusion in humans. We hypothesized it could evaluate murine myocardial perfusion before and after acute coronary ligation. MCE was performed before and after this experimental myocardial infarction (MI) in anesthetized mice by intravenous injection of contrast microbubbles and transthoracic echo imaging. Time-video intensity curves were obtained for the anterior, lateral, and septal myocardial walls. After MI, MCE defects were compared with the area of no perfusion measured by Evans blue staining. In healthy animals, intramyocardial contrast was visualized in all the cardiac walls. The anterior wall had a higher baseline video intensity (53 +/- 17 arbitrary units) than the lateral (34 +/- 13) and septal (27 +/- 13) walls (P < 0.001) and a lower increase in video intensity after contrast injection [50 +/- 17 vs. 60 +/- 24 (lateral) and 65 +/- 29 (septum), P < 0.01]. After MI, left ventricular (LV) dimensions were enlarged, and the shortening fraction was decreased. A perfusion defect was imaged with MCE in every mouse, with a correlation between MCE perfusion defect size (35 +/- 13%) and the nonperfused area by Evans blue (37 +/- 16%, y = 0.77x + 6.1, r = 0.93, P < 0. 001). Transthoracic MCE is feasible in the mouse and can accurately detect coronary occlusions and quantitate nonperfused myocardium.