This study was performed to test the hypothesis that increases in myocardial oxygen consumption (MVo2) and myocardial contractile function during exercise are flow limited. Studies were performed in 15 chronically instrumented normal dogs. MVo2 and regional percent systolic wall thickening were measured during control conditions and during maximal vasodilation produced by infusion of adenosine (20-75 micrograms.kg-1.min-1) or adenosine combined with nitroglycerin (0.4 micrograms.kg-1.min-1; TNG) into the left anterior descending coronary artery during a three-stage graded treadmill exercise protocol. Adenosine and adenosine plus TNG significantly increased coronary blood flow by 298 +/- 26 and 306 +/- 24%, respectively, at rest and by 134 +/- 7 and 145 +/- 9%, respectively, during the heaviest level of exercise (each P < 0.01). Adenosine and adenosine plus TNG increased MVo2 at rest, but this was associated with a parallel increase in heart rate, so that MVo2 per beat was not significantly changed. Systolic wall thickening was also not changed by hyperperfusion during resting conditions. However, MVo2 per beat was increased by 12 +/- 4% with adenosine and by 13 +/- 5% with adenosine plus TNG during moderate exercise and by 23 +/- 5% with adenosine and by 27 +/- 4% with adenosine plus TNG during the heaviest level of exercise (each P < 0.05). Systolic thickening of the full left ventricular wall did not change during hyperperfusion, but thickening in the subepicardial layer was increased by 14 +/- 3% with adenosine and 18 +/- 3% with adenosine plus TNG during the heaviest level of exercise (each P < 0.05). There was no difference in wall thickening between adenosine and adenosine plus TNG. These findings imply that the increases in MVo2 which occur during exercise are limited by coronary blood flow.