Repeated administration of highly purified eicosapentaenoic acid (as ethyl ester) resulted in a decrease in plasma triglycerides and high density lipoprotein (HDL) cholesterol. This was accompanied by a stimulation in the activities of carnitine palmitoyltransferase, fatty acyl-CoA oxidase and peroxisomal beta-oxidation in the liver. The results suggest that the triglyceride-lowering effect observed with eicosapentaenoic acid may be due to a reduced supply of fatty acids for hepatic triglyceride synthesis because of increased fatty acid oxidation. Eicosapentaenoic acid feeding marginally affected the triglyceride content of heart and mitochondrial and peroxisomal enzyme activities.