The addition of a fish oil supplement rich in n - 3 unsaturated fatty acids to a high cholesterol, high saturated fat (BT) diet for swine has been shown previously to result in modest lowering of plasma cholesterol levels and in marked retardation of atherogenesis. It has been suggested that the effect was due to the change in polyunsaturated (PUFA) to saturated fatty acid ratios (P/S) and that a supplement of PUFA of the n - 6 series might have the same effect as the fish oil. We have tested this hypothesis in swine fed an atherogenic diet by comparing the effect of a fish oil supplement producing a P/S ratio of 0.28 to that of corn oil in the same amount producing a ratio of 0.46. The P/S ratio of the atherogenic diet without supplements was 0.16. Thirteen young male Yorkshire swine were fed either BT alone (n = 4), BT + cod liver oil (n = 4) or BT + corn oil (n = 5) for 6 months and then killed for quantitative studies of atherosclerosis in the aortas and coronary arteries including lesion areas, number of lesion cells, and number of monocytes attached to endothelium. Plasma cholesterol levels were determined periodically and lipoproteins were separated terminally by density gradient ultracentrifugation, Pevikon block electrophoresis and immunoelectrophoresis. The fish oil supplement resulted in a 30% reduction in time-weighted average plasma cholesterol levels, and a marked shift in terminal lipoprotein patterns from predominantly apo B and E containing ones to predominantly apo B only ones. Atherogenesis was reduced by the fish oil supplement as judged by several morphometric criteria including size of lesions, number of lesion cells, and number of monocytes attached to lesion endothelium. The corn oil supplement produced no significant reductions in any of these variables from those in swine fed the atherogenic BT diet without the supplement. We conclude that the n - 3 fatty acid rich fish oil supplemented diet retarded atherogenesis, but that this effect was not shared by the corn oil supplemented diet which had an even higher P/S ratio.