Peroxidation reactions may cause many of the dysfunctions associated with aging. Accordingly, the 30-fold differences in aging rate among the mammalian species could be determined in part by peroxidation defense processes. This possibility was tested by measuring the spontaneous autoxidation of aerobically incubated brain and kidney tissue homogenates of 24 different mammalian species as a function of their maximum lifespan potential. Results show a statistically significant inverse correlation between both the rate of autoxidation and the amount of peroxidizable substrate with maximum lifespan potential. Kinetic analysis of the data indicates that the amount of peroxidizable substrate was the major factor determining the rate of autoxidation. For human tissues, antioxidants also appear to contribute to their unusually low sensitivity to peroxidation. These results support the hypothesis that aging may be caused in part by oxygen radicals initiating peroxidation reactions and that peroxidation defense processes are involved in governing the longevity of mammalian species.