Myocardial dysfunction may occur in areas remote from an acutely occluded coronary artery if those areas are served by a critically stenosed vessel. Although subendocardial hypoperfusion of such remote myocardium has been demonstrated in experimental preparations of this situation, this study was undertaken to determine whether actual reductions in subendocardial perfusion below control levels were necessary for such dysfunction to occur. A 20 mg dose of pentobarbital was injected into the left anterior descending artery (LAD) in 14 anesthetized dogs to create a large anterior regional wall motion abnormality without drawing significant collateral flow from the circumflex vascular bed. Circumflex subendocardial flow was found to rise during injections of pentobarbital and occlusion of the LAD (1.12 ± 0.38 and 1.17 ± 0.34 ml/min/g, respectively, vs control 0.91 ± 0.23 ml.min/g; p<.05) in the absence of circumflex stenosis. In the presence of circumflex stenosis, circumflex subendocardial flow fell during left anterior descending occlusion (0.59 ± 0.21 vs 0.89 ± 0.19 ml/min/g control; p<.01) but did not change during pentobarbital injections in the LAD (0.77 ± 0.36 ml/min/g). In the absence of circumflex stenosis, circumflex segment shortening increased during injection of pentobarbital or occlusion of the LAD (14.3 ± 4.9% and 14.4 ± 3.5%, respectively, vs 12.3 ± 3.3% control). In the presence of circumflex stenosis, it did not change (12.5 ± 4.0% pentobarbital, 11.8 ± 3.6 LAD occlusion vs 13.1 ± 4.0% control). We concluded that the presence of large regional wall motion abnormalities may increase the oxygen consumption of remaining myocardium and that dysfunction of that myocardium may result from relative hypoperfusion if blood flow cannot increase appropriately.