The authors studied the influence of active coronary vasomotion on transmural myocardial perfusion during tachycardia. Regional myocardial blood flow was estimated in chronically prepared awake dogs by injecting radioactive microspheres (7-10 μm in diameter) into the left atrium. Studies were performed during ventricular pacing at 100, 150, 200, and 250 beats/min under control conditions with intact coronary vasomotor tone, and during maximal coronary vasodilation induced by intravenous infusion of adenosine. During control conditions, mean myocardial blood flow was 1.27 ± 0.12 ml/min/g of myocardium at a heart rate of 100 beats/min, and increased regularly with increasing heart rates. Transmural myocardial perfusion remained essentially uniform as heart rates were increased from 100 to 250 beats/min. During administration of adenosine, mean myocardial blood flow increased to 5.49 ± 0.39 ml/min/g at a heart rate of 100 beats/min, and transmural myocardial perfusion was uniform. As heart rates were increased, flow to the subendocardium decreased as a linear function of heart rate while subepicardial flow was maintained so that the ratio of subendocardial-subepicardial flow fell from 1.00 at a heart rate of 100 beats/min to 0.40 at a heart rate of 250 beats/min. The reduction of subendocardial perfusion with increasing heart rate was most marked in the deepest myocardial layers. This rate-dependent decrease in subendocardial blood flow resulted in a decrease in mean myocardial blood flow with increasing heart rates (mean change at 250 beats/min = -18%; P < 0.05). These data indicate that active coronary vasomotion is necessary for maintenance of uniform transmural myocardial perfusion during tachycardia.