Oxidative atmospheric pollutants represent a significant stress and cause injury to both vertebrate and invertebrate species. In both, the biosurfaces of their respiratory apparatus are directly exposed to oxidizing pollutant-induced stresses. Respiratory-tract surfaces contain integrated antioxidant systems that appear to provide a primary defense against environmental insults caused by inhaled atmospheric reactive oxygen species (ROS) and reactive nitrogen species (RNS), whether gaseous or particulate. When the biosurface antioxidant defenses are overwhelmed, oxidative and nitrosative stress to the acellular and cellular components of the exposed biosurfaces can ensue via direct chemical reactions that lead to the induction of inflammatory, adaptive, injurious, and reparative processes. The study of model invertebrates (e.g., Drosophila) has a long history of yielding valuable insights into both fundamental biology and pathobiology. Mutants and/or transgenic insects, with specific alterations in key components of innate and/or adaptive antioxidant defense systems and immune genes, offer opportunities to dissect the complex systems that maintain respiratory tract surface defenses against environmental oxidants and the ensuing host responses. In this article, we use a comparative absfont approach to consider interactions of atmospheric oxidant pollutants with selected biosystems. We focused primarily on ozone (O(3)) as the pollutant, vertebrate and invertebrate respiratory tracts as the exposed biosystems, and nonenzymatic micronutrient antioxidants as significant contributors to overall antioxidant defense strategies. We present parallels among these diverse organisms with regard to their protective strategies against environmental atmospheric oxidants, with particular focus given to using the invertebrate Drosophila as a potentially useful model for vertebrate respiratory-tract responses to inhaled oxidants specifically and pollutants in general. We conclude that the insect respiratory system has considerable promise toward understanding novel aspects of vertebrate respiratory tract responses to inhaled oxidative environmental challenges.