This study investigates the interactive effects of chronic ethanol ingestion and exercise training on the antioxidant system and lipid peroxidation in cortex, cerebellum, medulla, striatum and hypothalamus of the rat brain. Exercise training (6.5 weeks) significantly increased superoxide dismutase (SOD) activity in striatum, the region associated with motor activity, but decreased SOD activity in other brain regions. Catalase (CAT) activity decreased significantly in hypothalamus, the region associated with behavior, due to exercise. The training significantly increased glutathione peroxidase (GSH-Px) activity in brain regions studied with the exception of cerebellum. In addition, glutathione reductase (GR) activity increased in brain regions, with the exception of medulla. The training significantly decreased malondialdehyde (MDA) levels in all brain regions studied, which is due to training adaptation. Ethanol (20%) (2.0 g kg -1 , p.o. for 6.5 weeks) significantly decreased SOD activity in all regions except cortex, CAT activity in cortex, striatum and hypothalamus, GSH-Px activity in cerebellum and GR activity in medulla. Similarly, ethanol significantly decreased the GSH level in cortex, medulla and striatum and the GSH/GSSG ratio in medulla and cerebellum. Conversely, ethanol significantly augmented GR activity in cortex, cerebellum and striatum. When ethanol and exercise were combined, there was significantly increased SOD and CAT activity in striatum, GSH-Px activity in cortex, striatum and hypothalamus and GR activity in cortex and striatum. The GSH level was significantly depleted in cortex, striatum and medulla. Combining training and ethanol also decreased MDA levels in medulla and cerebellum. In conclusion, the sensitivity of specific brain regions in reaction to chronic ethanol ingestion or training is a function of variability in antioxidant system activity. Thus, exercise training protects specific brain regions against ethanol-induced oxidative injury.