Relaxant responses to halothane and isoflurane were compared in helical strips of dog epicardial coronary arteries of different sizes: proximal large coronary arteries with outside diameters (OD) larger than 2.5 mm and distal small arteries with 0.7–0.9 mm OD. Responses to pharmacologic vasodilators, including nitroglycerin (NTG) and adenosine, were also studied for comparison. The relaxation induced by halothane in concentrations of 0.8–2.3% and by NTG (10−9–10−5M) was greater in proximal large coronary arteries than in distal small ones contracted with 20 mM KCl. In contrast, the relaxation by isoflurane (1.2–3.5%) and by adenosine (10−8–10−4M) was greater in small coronary arteries than in large ones. These results suggest that isoflurane is, like adenosine, preferentially a small artery dilator.