Male and female rats were exposed to depleted uranium acetate (DU) in drinking water at doses of 0, 75, or 150 mg/L for either 2 weeks or 6 months. After exposure, the animals were tested for behaviors in the open-field. After testing in the open-field, the brains were examined for levels of lipid oxidation using the thiobarbituric acid (TBA) assay. Behavioral differences (line crossing and rearing) were seen in male rats after 2 weeks exposure to DU in drinking water for the highest dose group. Increased brain lipid oxidation was seen for the highest dose group for both genders. Lipid oxidation levels correlated significantly with line crossing and rearing in the open-field. After 6 months exposure, behavioral differences for male rats in the open-field remained and expanded to include other behaviors (grooming, defecation, and urination). Female rats also demonstrated some behavioral changes after 6 months exposure. Lipid oxidation in the brain continued to be seen; however, these levels no longer correlated with open-field behaviors. These data suggest that DU is a toxin that crosses the blood-brain barrier, producing behavioral changes in male rats and lipid oxidation regardless of gender in as little as 2 weeks in the rat. Longer exposures to DU may produce greater behavioral changes but compensatory mechanisms may reduce the effects of lipid oxidation. Males appear to be more sensitive to the behavioral effects of DU.