It has been proposed that oxygen-derived free radicals are produced upon reperfusion of ischemic brain, and that they can cause tissue injury to the brain. Global ischemia/reperfusion insult to gerbil brain was produced by transient occlusion and release of both common carotid arteries. Oxidative DNA damage, as measured by the 8-hydroxy-2`-deoxyguanosine (B-OH-dG) level, was increased by ischemia/reperfusion insult Ischemia/reperfusion insult to gerbil brain did not cause any significant induction of antioxidant enzymes, such as superoxide dismutase, catalase, or a thiol-dependent protector protein. However, catalase activity was slightly decreased. These results suggest that ischemia/reperfusion insult to gerbil brain causes the DNA damage via the production of reactive oxygen species and that the antioxidant enzyme systems were not induced to prevent oxidative damage to DNA.