The incorporation of fatty acids from dietary fish oil was measured in obstructive atherosclerotic plaques removed from 11 patients fed fish oil, rich in omega-3 fatty acids, for 6-120 days before a planned arterial endarterectomy. The fatty acids of plasma and atheroma were analyzed with special reference to docosahexaenoic acid (DHA, 22:6) and eicosapentaenoic acid (EPA, 20:5), the principal omega-3 fatty acids of fish oil. The omega-3 fatty acid content increased greatly in plasma from 0.9% of fatty acids to 14.8% in cholesteryl esters, from 3.8% to 22.1% in phospholipids, and from 1.3% to 21.9% in triglycerides. The omega-3 fatty acid content of the atherosclerotic plaques was also greater when compared with that of plaques removed from 18 non-fish oil-fed controls. The omega-3 fatty acid in cholesteryl esters of the plaques was 4.9% in the experimental group versus 1.4% in control plaque, in phospholipids it was 8.8% versus 1.8%, and in triglycerides it was 4.7% versus 0.7% (p less than 0.001 for each lipid class). The two major omega-3 fatty acids (DHA and EPA) behaved differently. Compared with their respective plasma levels, relatively more DHA than EPA was deposited into the plaques. Whereas the increase of omega-3 fatty acids in plasma reached a plateau 3 weeks after initiation of fish oil feeding, a linear increase in plaque omega-3 fatty acids continued with time. As a result of the changes in fatty acid composition, the lipid classes of both plasma and plaque had a higher unsaturation index in the fish oil-fed group.(ABSTRACT TRUNCATED AT 250 WORDS)