The objective of this study was to explore the basis of variations in the life span and metabolic potential, i.e., total amount of energy consumed during life, between different species, in context of the free radical hypothesis of aging. A comparison was made between the house mouse (Mus musculus) and the white-footed mouse (Peromyscus leucopus): the latter has > 2-fold greater life span and metabolic potential than the former. Longer life span and higher metabolic potential of Peromyscus were associated with low rates of mitochondrial O2.- and H2O2 generation, higher activities of catalase and glutathione peroxidase and low levels of protein oxidative damage as well as low susceptibility to oxidative damage in response to experimental oxidative stress. Results support the role of oxidative stress in aging.