O-3-induced changes in growth, oxidative damage to protein, and specific activities of certain antioxidant enzymes were investigated in wheat plants (Triticum aestivum L. cv Roblin) grown under ambient or high CO2. High CO2 enhanced shoot biomass of wheat plants, whereas O-3 exposure decreased shoot biomass. The shoot biomass was relatively unaffected in plants grown under a combination of high CO2 and O-3. O-3 exposure under ambient CO2 decreased photosynthetic pigments, soluble proteins, and ribulose-1,5-bisphosphate carboxylase/oxygenase protein and enhanced oxidative damage to proteins, but these effects were not observed in plants exposed to O-3 under high CO2. O-3 exposure initially enhanced the specific activities of superoxide dismutase, peroxidase, glutathione reductase, and ascorbate peroxidase irrespective of growth in ambient or high CO2. However, the specific activities decreased in plants with prolonged exposure to O-3 under ambient CO2 but not in plants exposed to O-3 under high CO2. Native gels revealed preferential changes in the isoform composition of superoxide dismutase, peroxidases, and ascorbate peroxidase of plants grown under a combination of high CO2 and O-3. Furthermore, growth under high CO2 and O-3 led to the synthesis of one new isoform of glutathione reductase. This could explain why plants grown under a combination of high CO2 and O-3 are capable of resisting O-3-induced damage to growth and proteins compared to plants exposed to O-3 under ambient CO2.