One mechanism for the eventual decompensation of the hypertrophied to the failing heart may involve inadequate myocardial perfusion. In support of this concept are studies in experimental models of both right and left ventricular hypertrophy and failure. These studies demonstrate blunted reactive hyperemic responses to brief periods of coronary artery occlusion, and reduced vasodilation in response to adenosine, when the most severe impairment in coronary reserve occurs in the subendocardium. During exercise, in the hypertrophied and failing heart, the normal coronary vasodilator response is also blunted. Although endocardial/epicardial blood flow ratios are depressed in congestive heart failure under baseline conditions, the endocardial/epicardial ratio decreases further with stress, e.g., during either adenosine or reactive hyperemia. These data suggest that one mechanism of failure of the severely hypertrophied heart may involve inadequate coronary perfusion to the subendocardium.