The effects of n-3 fatty-acid supplementation on serum lipids, platelet aggregation, and the development of atherosclerotic lesions were studied in the cholesterol-fed rabbit. Serum total cholesterol and LDL cholesterol values were significantly reduced in comparison with those of the nonsupplemented cholesterol-fed group (p < 0.005, p < 0.0025, respectively), though still higher than those of the control group (p < 0.0025, p < 0.0125 respectively). Platelet aggregation was reduced below that of the cholesterol-fed and the control levels (p < 0.0005, p < 0.0025, respectively). The endothelial injury encountered in cholesterol-fed rabbits was inhibited in the supplemented group. It is concluded that n-3 fatty acids suppress atherogenesis in this animal model by interfering with platelet aggregation and lipid metabolism.