The oxidative stress theory of aging predicts a low degree of fatty acid unsaturation in tissues of longevous animals, because membrane lipids increase their sensitivity to oxidative damage as a function of their unsaturation. Accordingly, the fatty acids analyses of liver mitochondria from eight mammals, ranging in maximum life span from 3.5 to 46 years, show that the total number of double bonds and the peroxidizability index are negatively correlated with maximum life span (r = −0. 88, P < 0.003; r = −0.87, P < 0.004, respectively). This is not due to a low content of unsaturated fatty acids in longevous animals, but mainly to a redistribution between kinds of the polyunsaturated n–3 fatty acids series, shifting from the highly unsaturated docosahexaenoic acid (r = −0.89, P < 0.003) to the less unsaturated linolenic acid (r = 0.97, P < 0.0001). This redistribution pattern strongly suggests the presence of a constitutively low Δ6-desaturase activity in longevous animals (r = −0.96, P < 0.0001). Thus, it may be proposed that, during evolution, a low degree of fatty acid unsaturation in liver mitochondria may have been selected in longevous mammals in order to protect the tissues against oxidative damage, while maintaining an appropriate environment for membrane function.