Immobilization stress of male Sprague-Dawley rats induces oxidative damage to lipid, protein, and DNA in the brain, Significant increases in lipid peroxidation were found in the cerebral cortex, cerebellum, hippocampus, and midbrain compared to the unstressed controls, Significant increases in levels of protein oxidation were also found in the cortex, hypothalamus, striatum, and medulla oblongata, Oxidative nuclear DNA damage increased after stress in all brain regions, although only the cerebral cortex showed a significant increase, Depletion of glutathione showed some stimulation to oxidative damage in the unstressed control and stressed animals, Further studies of the mitochondrial and cytosol fractions of cerebral cortex demonstrated that mitochondria showed a significantly greater increase in lipid peroxidation and protein oxidation than cytosol, Data from plasma and liver showed oxidative damage similar to that of the brain, These findings provide evidence to support the idea that stress produces oxidants, and that the oxidative damage in stress could contribute to the degenerative diseases of aging, including brain dysfunction.