Epidemiological studies in Greenland Eskimos led to the hypothesis that marine oils rich in n-3 fatty acids (also referred to as omega (omega)-3 fatty acids) are hypolipidemic and ultimately antiatherogenic. Metabolically controlled trials in which large amounts of fish oil were fed to normal volunteers and hyperlipidemic patients showed that these fatty acids (FAs) are effective at lowering plasma cholesterol and triglyceride levels. Although more recent trials using smaller, more practical doses of fish oil supplements have confirmed the hypotriglyceridemic effect, they have shown little effect on total cholesterol levels; hypertriglyceridemic patients have even experienced increases in low density lipoprotein cholesterol (LDL-C) levels of 10-20% while taking n-3 FA supplements. Discrepancies among fish oil studies regarding the effects of n-3 FAs on LDL-C levels may be understood by noting that, in the majority of studies reporting reductions in LDL-C levels, saturated fat intake was lowered when switching from the control diet to the fish oil diet. When fish oil is fed and saturated fat intake is constant, LDL-C levels either do not change or may increase. Levels of high density lipoprotein cholesterol have been found to increase slightly (about 5-10%) with fish oil intake. Plasma apolipoprotein levels change in concert with their associated lipoprotein cholesterol levels. Although the decrease in triglyceride levels appears to result from an inhibition in hepatic triglyceride synthesis, the mechanisms leading to the increases in LDL and HDL have not been determined. Finally, fatty fish or linolenic acid may serve as alternative sources of long-chain n-3 FAs, but further studies will be needed to document their hypolipidemic and/or antiatherogenic effects.