A critical review of the literature on the effects of vitamin E and selenium deficiences on unsaturated fatty acid metabolism reveals that some of these effects are inconsistent with the antioxidant hypothesis of these nutrients as their only biological function. On the basis of these data it is proposed that vitamin E and selenium play a role in the desaturation of n-3 and n-6 polyunsaturated fatty acids by participating in the microsomal electron transport chain and in a proposed peroxidase moiety of the desaturase complex, respectively. A re-interpretation of the experimental literature in terms of the proposed hypothesis is provided, with some suggestions to test its main tenets.