Intracerebroventricular t-butyl hydroperoxide has been reported to induce damage to many types of brain cells. t-Butyl hydroperoxide administration increases glutathione disulfide levels and decreases levels of glutathione. Young adult mice may be more protected from t-butyl hydroperoxide than mature mice due to their higher glutathione levels, even after the adminstration of t-butyl hydroperoxide. This leads to our current study, investigating glutathione peroxidase and glutathione disulfide reductase in 2-mo-old and 8-mo-old mice. Furthermore, malondialdehyde levels were measured with the thiobarbituric acid assay and compared between the two age groups. Mature mice detoxify glutathione disulfide less readily than young adult mice. Glutathione disulfide reductase activity increases in young adult mice after t-butyl hydroperoxide administration, but not in mature mice. Glutathione peroxidase activity is significantly lower in 8-mo-old than 2-mo-old mouse striatum after t-butyl hydroperoxide administration. Furthermore, malondialdehyde levels in the 8-mo-old striatum increase significantly 20 min after t-butyl hydroperoxide administration. This suggests that age plays a factor in protective mechanisms that are involved in oxidative stress in the brain.