Our studies in the cholesterol-fed rabbit model indicate that moderate alcohol consumption reduces the risk of restenosis by preventing low-density lipoprotein (LDL) oxidation. Eighteen hypercholesterolemic rabbits underwent arterial injury by Fogerty balloon endothelial denudation of iliac arteries. Two weeks later, balloon angioplasty of atherogenic or atherosclerotic arterial segments was performed. Nine rabbits (control) received water ad lib, whereas nine rabbits (moderate alcohol treated) received an average of 2.5 ml alcohol per 500 ml water daily, from the day of feeding hypercholesterolemic diet until they were killed, 10 weeks later. There was a 26% increase in lumen size of the moderate alcohol-treated group compared with the control group. The percentage neointima formation (NI) values of the moderate alcohol-treated and control groups were 77 +/- 2.1 and 61 +/- 1.9, respectively (p < 0.001). The lumen/neointima (L/NI) ratio of the moderate alcohol-treated group was 0.71 +/- 0.07 compared with the control group, 0.33 +/- 0.04 (p < 0.001). The number of foam cells in the moderate alcohol-treated group was threefold less than the control group [i.e., 1.4 +/- 0.4 and 3.9 +/- 0.8, respectively (p = 0.005)]. The arterial lesion malondialdehyde (MDA) values of the control and the moderate alcohol-treated groups were 13.6 +/- 2.8 and 4.4 +/- 0.5 (p = 0.004), respectively. By radioimmunoassay, the moderate alcohol-treated group had less macrophage chemotactic protein-1 (MCP-1; 3,277 cpm/microg protein) and platelet-derived growth factor (PDGF; 2,261 cpm/microg protein) compared with the controls (MCP-1, 4,529 cpm/microg protein; PDGF, 3,583 cpm/microg protein). Thus we conclude that low concentrations of alcohol reduce neointimal formation, and the extent of lipid oxidation, the number of foam cells in the neointimal area and may decrease the expression of MCP-1 and PDGF by reducing LDL oxidation in an animal model of postangioplasty restenosis.