Apolipoprotein E (Apo-E) is linked to the pathogenesis of Alzheimer's disease. Apo-E deficient mice have increased lipid peroxidation in plasma. In the present study we examined two markers of oxidative stress in brains of Apo-E deficient mice. The ratios of 2,3 and 2,5 dihydroxybenzoic acid (DHBA)/salicylate, an index of hydroxyl radical generation, were unchanged except for an increase in 2.5-DHBA/salicylate in the cerebellum. 3-Nitroxyrosine is a marker for nitration of proteins produced by peroxynitrite. Concentrations of 3-nitrotyrosine were significantly increased in the cerebral cortex, hippocampus, brainstem and cerebellum of Apo-E deficient mice. These results suggest the Apo-E may modulate oxidative stress produced by peroxynitrite.