This study was carried out to test the hypothesis that α1-adrenergic activation during exercise causes preferential vasoconstriction of subepicardial coronary resistance vessels, thereby augmenting blood flow to the subendocardium. Studies were performed in 7 dogs in which left ventricular hypertrophy was produced by banding the ascending aorta at 6-9 weeks of age. Animals were studied at approximately 1 year of age when the left ventricular/body weight ratio was 7.7±0.3 g/kg (mean±SE). Left anterior descending (LAD) coronary artery flow was measured with a Doppler velocity flow probe at rest and during a three-stage graded treadmill exercise protocol. The transmural distribution of myocardial blood flow was assessed with radioactive microspheres. Coronary blood flow increased progressively as a function of heart rate and rate-pressure product in response to exercise. In contrast to normal dogs which maintain preferential blood flow to the subendocardium (ENDO) relative to the subepicardium (EPI) during exercise, the ENDO/EPI flow ratio in the hypertrophied left ventricles was 0.88±0.10 during exercise. Selective α1-adrenergic blockade by infusion of prazosin (10 μg/kg) into the LAD decreased mean aortic pressure during exercise from 86±6 to 76±4 mmHg (p<0.05), but did not change coronary pressure, heart rate, left ventricular systolic or end-diastolic pressures, or LVdP/dtmax. Coronary blood flow was not significantly altered by prazosin at rest, but was progressively increased during increasing levels of exercise levels. During the heaviest level of exercise prazosin caused a 22±3% increase in mean myocardial blood flow which was similar in all transmural layers, with no change in the transmural distribution of perfusion (ENDO/EPI=0.85±0.09). These findings demonstrate that α1-adrenergic vasoconstrictor tone limits blood flow during exercise in the hypertrophied left ventricle, but do not support the concept that α1-adrenergic activation augments perfusion of the subendocardium during exercise. © 1995 Steinkopff Verlag.