In chronically instrumented conscious dogs, hydralazine (30–300 μg/kg) and nitroglycerin (NTG 0.03–10 μg/kg) dose-dependently dilated large epicardial coronary arteries. Simultaneously, hydralazine also dose-dependently dilated small coronary arteries, whereas a similar effect was observed only after NTG ≥0.3 μg/kg. When large coronary arteries were deendothelialized by a balloon angioplasty catheter, dilation of large coronary arteries in response to acetylcholine (ACh 0.3 μg/kg) and to reactive hyperemia was reduced by 87 and 95%, respectively. In contrast, vasodilation of large coronary arteries induced by hydralazine and NTG was only minimally and similarly affected (-19% for both drugs). These findings demonstrate that in vivo hydralazine-induced dilation of large coronary arteries is endothelium independent.