Exogenously hypercholesterolemic (ExHC) rats were fed on an atherogenic diet supplemented with 1% each of either ethyl ester docosahexaenoic acid [EE-DHA, 22:6(n-3)], ethyl ester eicosapentaenoic acid [EE-EPA, 20:5(n-3)] or safflower oil (SO) for 6 months. The rats fed on the diets containing EE-EPA or EE-DHA, compared with those fed on SO, had lower serum cholesterol and triacylglycerol levels, less aggregation of platelets and slower progress of intimal thickening in the ascending aorta. Relative to the SO-fed rats, both of the (n-3) fatty acid-fed rats had a significantly reduced proportion of arachidonic acid in the platelet and aortic phospholipids, and lower production of thromboxane A2 by platelets and of prostacyclin by the aorta. These results suggest that EPA and DHA are similarly involved in preventing atherosclerosis development by reducing hypercholesterolemia and modifying the platelet functions.