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In a study involving mice, the antioxidant alpha-lipoic acid was found to attenuate cognitive dysfunction induced by radiation. Mice exposed to whole-body X-irradiation (6Gy) were found to have impairment in memory and motor activities. When mice were given acute intraperitoneal treatment with alpha-lipoic acid prior to irradiation, the effects of the radiation on cognitive function were significantly attenuated. Specifically, ALA was found to protect against radiation-induced augmentation of protein carbonyls and TBARS in the cerebellum and deficit of total, nonprotein, and protein-bound sulfhydryl contents of cerebellum and plasma ferric reducing power. Furthermore, compared to untreated mice exposed to radiation, the mice treated with ALA were found to have an intact cytoarchitecture of the cerebellum and higher counts of Purkinje cells and granular cells. The results of this study suggest that alpha-lipoic acid has potent neuroprotective properties and may protect against radiation-induced cognitive dysfunction and cerebellar oxidative stress in mice.