Background: Smooth muscle cell (SMC) hyperplasia is an important mechanism of restenosis after coronary angioplasty and the primary mechanism of restenosis within coronary stents. Ethanol has been shown to reduce the response of SMCs to local growth stimulants in vitro. This study was carried out to determine whether local delivery of ethanol solution could reduce intimal hyperplasia induced by balloon injury. Methods and Results: Three groups of juvenile domestic pigs underwent oversized balloon dilation injury of the left anterior descending and left circumflex coronary arteries. Immediately after the balloon injury, one of the arteries was randomized to local delivery of 15% ethanol with a local delivery balloon catheter, and the other received no further treatment. Histological and morphometric studies were carried out at 2 weeks in group 1 (n=16) and at 4 weeks in group 2 (n=10). In the third group (n=15), animals were killed at days 4, 8, and 14 after balloon injury, and coronary artery segments were studied by immunohistochemical staining against proliferating cell nuclear antigen (PCNA) and bromodeoxyuridine (BrdU). Histological injury scorns were not different between the ethanol-treated and untreated arterial segments in either group 1 or 2. The neointimal areas were significantly smaller in the ethanol-treated arterial segments than in the untreated segments (0.25±0.08 versus 0.57±0.08 mm2, P=.004, at 2 weeks; 0.33±0.05 versus 0.54±0.07 mm2, P=.03, at 4 weeks). SMC proliferative activity was significantly lower in ethanol-treated arteries than in untreated arteries at 4 and 8 days after injury by BrdU and PCNA staining. Conclusions: Local delivery of 15% ethanol solution to pig coronary arteries significantly decreased the SMC proliferative activity and neointimal formation induced by balloon dilation injury.