The general objective of this investigation was to examine the relationship between oxygen free radicals and the aging process. Comparisons of antioxidant defenses were made in six different mammalian species, namely, mouse, rat, guinea pig, rabbit, pig and cow, which range from 3.5 to 30 years in their maximum life span potential (MLSP). Activities of superoxide dismutase (SOD), catalase, and glutathione peroxidase, and concentration of glutathione were measured in the liver, the heart, and the brain. SOD and catalase activities were positively correlated whereas glutathione concentration was negatively correlated with MLSP. Glutathione peroxidase activity exhibited a variable pattern: being positively correlated with MLSP in the brain and negatively correlated in the liver and the heart. In each organ, MLSP was correlated with relatively high levels of one or two of the above antioxidants and low levels of the other antioxidants, indicating the possibility of a compensatory balance among various components of the antioxidant system. No obvious pattern of a relationship was detectable between the overall level of antioxidant defenses and MLSP among the mammalian species examined. The implications of this finding concerning the role of oxidative stress in the aging process and the free radical hypothesis of aging are discussed.