In the hypertrophied heart, increased extravascular forces acting to compress the intramural coronary vessels might require augmentation of metabolic vasodilator mechanisms to maintain adequate coronary blood flow. Vascular smooth muscle ATP-sensitive potassium (K⁺_ATP) channel activity is important in metabolic coronary vasodilation, and adenosine contributes to resistance vessel dilation in the hypoperfused heart. Consequently, this study was performed to determine whether K⁺_ATP channels and adenosine have increased importance in exercise-induced coronary vasodilation in the hypertrophied left ventricle. Studies were performed in dogs in which banding of the ascending aorta had resulted in a 66% increase in left ventricular mass in comparison with historic normal animals. Treadmill exercise resulted in increases of coronary blood flow that were linearly related to the increase of heart rate or rate-pressure product. During resting conditions, K⁺_ATP channel blockade with glibenclamide caused a 17 ± 5% decrease in coronary blood flow, similar to that previously observed in normal hearts. Unlike normal hearts, however, glibenclamide blunted the increase in coronary flow that occurred during exercise, causing a significant decrease in the slope of the relationship between coronary flow and the rate-pressure product. Adenosine receptor blockade with 8-phenyltheophylline did not alter coronary blood flow at rest or during exercise. Furthermore, even after K⁺_ATP channel blockade with glibenclamide, the addition of 8-phenyltheophylline had no effect on coronary blood flow. This finding was different from normal hearts, in which the addition of adenosine receptor blockade after glibenclamide impaired exercise-induced coronary vasodilation. The data suggest that, in comparison with normal hearts, hypertrophied hearts have increased reliance on opening of K⁺_ATP channels to augment coronary flow during exercise. Contrary to the initial hypothesis, however, adenosine was not mandatory for exercise-induced coronary vasodilation in the hypertrophied hearts either during control conditions or when K⁺_ATP channel activity was blocked with glibenclamide.