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Oxidative damage was measured by analyzing the production of hepatic reactive oxygen species (ROS), the activity of superoxide dismutase (SOD), and the content of malondialdehyde (MDA). DNA damage was measured by single\u2010cell gel electrophoresis (comet assay). After 3 days of exposure, significant differences in ROS production could only be seen between the control and the highest dosage group (10 mg\/kg BW d), although after 7 days of treatment, ROS production increased in a dose\u2010dependent manner. SOD activity increased with dosage after 3 days of exposure and decreased with dosage after 7 days of exposure. TBT also induced significant production of MDA after 7 days of exposure. The changes in ROS, SOD, and MDA found in this study suggest that the antioxidative systems of rats were activated by TBT in the first 3 days of exposure but had become exhausted by 7 days of exposure. In the comet assay, the number of cells with damaged DNA in rats treated with TBT increased with dosage of TBT. The most likely mechanism of the DNA breakage induced by TBT is oxidative damage. It can be concluded that exposure of TBT can promote both oxidative and DNA damage in mammals <jats:italic>in vivo.<\/jats:italic> \u00a9 2006 Wiley Periodicals, Inc. 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