Although myocardial contrast echocardiography accurately demarcates area at risk during total coronary occlusion, the ability of MCE to delineate area at risk in the presence of residual antegrade flow is unknown. We hypothesized that perfusion defects in myocardial segments supplied by severe coronary stenoses with residual antegrade flow could be detected by MCE using intravenous FS069. We studied 13 open-chest dogs using an intravenous injection of FS069 during intermittent harmonic imaging. Images were collected at baseline, during acute ischemia with residual antegrade flow, physiologic hyperemia (release of stenosis), and total coronary occlusion. Regional myocardial blood from was assessed using colored microspheres. MCE risk area during acute ischemia with residual antegrade flow and total occlusion was planimetered and compared with pathologic risk area (area unstained by monastral blue). Background-subtracted peak video-intensity in the risk area was assessed for all flow states. Regional myocardial blood flow confirmed expected flow states, being significantly greater during physiologic hyperemia (4.16 +/- 1.22 ml/min/g) than at baseline (0.71 +/- 0.19 ml/min/g) and significantly diminished during coronary stenosis with residual antegrade flow (0.20 +/- 0.16 ml/min/g) and total occlusion (0.09 +/- 0.06 ml/min/g; P < 0.0001). Myocardial risk area by MCE during coronary stenosis with residual antegrade flow correlated well with pathologic risk area determined by monastral blue staining (r = 0.86). Peak videointensity during coronary stenosis (111 +/- 27) was significantly less than at baseline (157 +/- 50) but greater than during total occlusion (81 +/- 34; P < 0.0001). In conclusion, intravenous FS069 in conjunction with intermittent harmonic imaging delineates area at risk in ischemic myocardium supplied by a coronary stenoses with residual antegrade flow. The presence of a perfusion defect on MCE does not necessarily imply that the coronary artery is totally occluded.