The physiological decline that occurs with aging is thought to result, in part, from accumulation of oxidative damage produced by reactive oxygen species (ROS) generated during normal metabolism. Two genetic mouse models of aging, the Ames dwarf and growth hormone (GH) transgenic, suggest that hormone levels may play a role in antioxidative defense and aging. To explore this possibility, catalase (CAT), an enzyme involved in elimination of ROS, was evaluated in long-lived dwarf and short-lived transgenic mice. Catalase activity and/or protein was significantly elevated in livers from dwarf mice at 3, 6, 13-15, and 24 months of age when compared to age-matched wild type mice. In contrast, a 50 and 38% reduction (P<0.05) in CAT protein was observed in 3 and 10 to 12 month old GH transgenics respectively, when compared to wild type mice. Kidneys from old dwarf mice exhibited significantly increased CAT activity (22%), protein (16%) and mRNA expression (59%) compared to wild type mice. Conversely, kidneys from GH transgenic mice showed reductions in CAT activity. The results of this study suggest that hormonal status modulates antioxidative mechanisms and that CAT is important in overall defense capacity with respect to lifespan in both decelerated (dwarf) and accelerated (transgenic) mammalian models of aging.