Ozone, the major oxidant pollutant in photochemical smog, causes toxic epithelial injury in the nasal and tracheobronchial airways of laboratory animals and people. Epidemiologic studies suggest that children may be more susceptible to the respiratory health effects of ozone exposure than adults. The majority of children in the United States live in areas in which the atmospheric ozone concentration exceeds the current National Ambient Air Quality Standard for this pollutant. Repeated exposure to high ambient levels of ozone induces site-specific rhinitis, mucous cell metaplasia, and epithelial hyperplasia in the nasal airways of adult, laboratory monkeys and rats. These remodeling events in the nasal airways of adult monkeys and rats are associated with an altered response to subsequent ozone challenge, and thus may serve as a protective adaptation. Low molecular weight antioxidants, such as the tripeptide glutathione (GSH), in the nasal epithelium and the overlying epithelial lining fluid (ELF) are regarded as the first line of defense against these and other inhaled oxidant pollutants. Recent studies have also implicated GSH in the development of pulmonary tolerance to ozone-induced injury, and in the pathogenesis of oxidant-mediated cell proliferation. Few studies have examined the effects of ozone exposure on the developing nasal airways of immature animal models. The overall goal of these experiments was to test the hypothesis that the site-specificity and temporal pattern of ozone-induced nasal epithelial remodeling in immature rats and infant monkeys is related to the local regulation of intracellular GSH. Infant, male rhesus macaques were exposed episodically to repeated cycles of ozone (0.5 ppm) and filtered air (0 ppm) for two or five months. The time-course of morphologic and immunohistochemical events comprising this ozone-induced nasal epithelial injury and repair were determined, and these were compared to site-matched changes in the steady-state levels of GSH in the nasal mucosa. In addition, a whole-animal inhalation study was conducted using immature Fischer 344 (F344) rats to determine the role of GSH in ozone-induced epithelial hyperplasia in the developing nasal airways of rats. Immature male F344 rats were exposed to three consecutive days of ozone (0.8 ppm) or filtered air. Infant monkeys episodically exposed to ozone for 5 months developed acute rhinitis, epithelial hyperplasia, and squamous metaplasia in the anterior nasal cavity. These animals also exhibited a significant increase in intracellular GSH concentration in the nasal mucosa corresponding to the site of remodeling. GSH concentration was positively correlated with the epithelial numeric cell density following filtered air or ozone exposure. In immature rats, ozone caused epithelial hyperplasia in the anterior nasal airways. However, unlike infant monkeys, the ozone-induced epithelial hyperplasia in immature rats was not associated with a local increase in GSH concentration. Furthermore, GSH depletion had no effect on ozone-induced cell proliferation. In conclusion, ozone-induced epithelial hyperplasia in the nasal airways is temporally correlated with local increases in mucosal GSH concentrations. However, ozone-induced hyperplasia in the nasal airways of rats is not a GSH-dependent phenomenon. Furthermore, since GSH upregulation is not unique to sites of injury in the nasal airways, other factors (e.g., interactions with other nasal antioxidants) must also contribute to the site-specificity of ozone-related nasal injury and repair.