The oxygen and glucose uptake, lactate formation, ATP/ADP and NADH/NAD ratios and incorporation of [14C]acetate and [14C]linolenic acid into lipids of early fatty streaks and more advanced complicated atherosclerotic lesions of human aorta were determined during aerobic and hypoxic incubation. Compared with grossly normal appearing sections of the aorta in intima and media preparations of early fatty streaks the oxygen uptake was increased while that in further developed atheroma was slightly diminished. Under aerobic incubation conditions the metabolic state of fatty streaks and atheroma was characterized by increased lactate formation, NADH/NAD ratio and incorporation of [14C]acetate and [14C]linolenic acid into the lipids, but by a lowered ATP/ADP ratio. More pronounced changes in these metabolic parameters were observed when the aortic tissue segments were incubated under hypoxic conditions. The analysis by argentation TLC of fatty acid methylesters derived from total lipids of aerobically incubated fatty streaks revealed an increased incorporation of [14C]acetate into the highly unsaturated long-chain fatty acids. In developed atherosclerotic lesions and in hypoxia the incorporation of radioacetate into the polyunsaturated fatty acids and the formation of 20:4 fatty acid from [14C]linolenic acid were, in contrast to the above finding, decreased while the synthesis of eicosatrienoic acid was increased. This finding suggests a block in the desaturation step of linoleic into 20:4 fatty acid in further developed atheroma and in hypoxia. In aerobically incubated atherosclerotic lesions and in hypoxia the palmitic acid was synthesized mainly by chain elongation while in grossly normal areas of the aorta at least part of this acid was synthesized de novo.