Studies in heart and nonsynaptic brain mitochondria from two mammals and three birds showthat complex I generates oxygen radicals in heart and nonsynaptic brain mitochondria in States4 and 3, whereas complex III does it only in heart mitochondria and only in State 4. Theincrease in oxygen consumption during the State 4 to 3 transition is not accompanied by aproportional increase in oxygen radical generation. This will protect mitochondria and tissuesduring bursts of activity. Comparisons between young and old rodents do not show a consistentpattern of variation in mitochondrial oxygen radical production during aging. However, allthe interspecies comparisons performed to date between different mammals, and betweenmammals and birds, agree that animals with high maximum longevities have low rates ofmitochondrial oxygen radical production, irrespective of the value of their basal specificmetabolic rate. The sites and mechanisms allowing this, the recently described low degree ofmembrane fatty acid unsaturation of longevous animals, and their relation to longevity andaging are discussed.