Vitamin E inhibits oxidative processes in living tissues. We produced vitamin E-deficient mice by feeding them a vitamin E-deficient diet to verify the influence of chronic vitamin E deficiency on cognitive function. We measured cognitive function over a 5-d period using the Morris water maze task, as well as antioxidant enzyme activity and lipid peroxidation in discrete brain regions, and total serum cholesterol content. Three- and six-mo-old vitamin E-deficient and age-matched control mice were used. In addition, 24-mo-old mice were used as an aged-model. In the 3-mo-old mice, cognitive function in the vitamin E-deficient (short-term vitamin E-deficient) group was significantly impaired compared to age-matched controls. Although the lipid peroxidation products in the cerebral cortex, cerebellum and hippocampus did not significantly differ in 3-mo-old mice, the levels in the 6-mo-old vitamin E-deficient (long-term vitamin E-deficient) mice were significantly increased compared to age-matched controls. Serum cholesterol content was also significantly increased in the short- and long-term vitamin E-deficient mice compared to their respective age-matched controls. These results indicate that chronic vitamin E deficiency may slowly accelerate brain oxidation. Thus, vitamin E concentrations may need to be monitored in order to prevent the risk of cognitive dysfunction, even under normal conditions.