In the experimental studies reported in this review, dietary omega-3 fatty acids from fish and fish oil had profound hypolipidemic effects in normal subjects and in hypertriglyceridemic patients with combined hyperlipidemia (type IIb) and type V hyperlipidemia. In these studies, 68 adults participated in carefully controlled metabolic experiments. In all subjects and patients, there were marked reductions in plasma cholesterol and triglyceride concentrations, with triglyceride lowering being especially great. There were also reductions in VLDL, chylomicrons, remnants, LDL, apo B, and apo E. The HDL changes were inconstant and varied from subject to subject. Whereas the mechanism of the hypolipidemic action of the omega-6-rich vegetable oils containing linoleic acid, such as corn or safflower oil, still remains obscure, the mechanism of action of the omega-3 fatty acids in fish oil has been well documented within a few years of their use as hypolipidemic agents. The synthesis of triglyceride and VLDL in the liver is greatly reduced by omega-3 fatty acids. At the same time, the turnover of VLDL in plasma is greatly shortened. LDL production is decreased. Combined with other dietary manipulations, such as a reduction in saturated fat and dietary cholesterol, the use of omega-3 fatty acids to treat hyperlipidemic and especially hypertriglyceridemic patients would appear to have a well-supported rationale. Further studies are required to delineate exact doses and precise indications for different types of hyperlipidemia and to differentiate the effects of, if any, the two major omega-3 fatty acids in fish oil, EPA and DHA. Coupled with the known antithrombotic actions of omega-3 fatty acids from fish oil because of changes in prostaglandin secretion and platelet function, these hypolipidemic effects would appear to have an important potential role in the control of coronary heart disease and other atherosclerotic disorders.