Purpose: Myocardial blood volume should be decreased depending on the extent of myocardial necrosis. However, it is not known whether the flow speed remains constant in cases with myocardial infarction and without any coronary stenosis, independent from the severity of myocardial necrosis. To examine this relationship, diffuse myocardial infarction was modeled by stepwise injection of microspheres (MS) , and myocardial blood volume and blood flow velocity were evaluated by myocardial contrast echocardiography (MCE) . Methods: The subjects were eight open-chest dogs. MSs (average diameter 100亮m) were injected into the left circumflex artery to model four stages of diffuse myocardial infarction during monitoring of coronary flow volume. Real-time MCE was examined at rest and after ATP administration. The A and β values of the replenishment curve were measured at each stage. Results: Although coronary flow volume did not decrease until the 4th stage at rest (20.8, 21.8, 19.0, 13.4, 9.2 ml/min at control and 1st to 4th stages, respectively) , it deteriorated stepwisely after ATP administration (47.6, 39.0, 31.0, 20.4, 11.6 ml/min) , resulting in deterioration of coronary flow reserve (2.28, 1.83, 1.65, 1.53, 1.23) . At rest, the A value decreased concomitantly with the dose of the MS injection, indicating the decrement of myocardial blood volume (111±8.7, 104±9.5, 90±11.9, 74±19.2, 56±31.9) . However, the β value did not change until a high dose of MSs (0.71±0.22, 0.89±0.27, 0.65±0.25, 0.62±0.33, 0.29±0.18) . On the other hand, after ATP administration, the β value decreased significantly with progression of MS load (2.07±1.34 at baseline, 1.56±0.92, 1.18±0.78, 0.87±0.47, 0.34±0.31) , indicating progressive deterioration of β reserve. Conclusions: Coronary flow reserve deteriorates concomitantly with progression of myocardial ischemia, even in the absence of coronary artery stenosis.