1-Nitronaphthalene and ozone are cytotoxic air pollutants commonly found as components of photochemical smog. The mechanism of toxicity for 1-NN involves bioactivation by cytochrome P450s and subsequent adduction to proteins. Previous studies have shown that 1-nitronaphthalene toxicity in the lung is considerably higher in rats following long-term exposure to ozone compared to the corresponding filtered air exposed control rats. The aim of the present study was to establish whether long-term exposure to ozone alters the susceptibility of nasal mucosa to the bioactivated toxicant, 1-nitronaphthalene. Adult male Sprague-Dawley rats were exposed to filtered air or 0.8 ppm ozone for 8 hours per day for 90 days, followed by a single treatment with 0, 12.5, or 50.0 mg/kg 1-nitronaphthalene by intraperitoneal injection. The results of the histopathological analyses show that the nasal mucosa of rats is a target of systemic 1-nitronaphthalene, and that long-term ozone exposure markedly lessens the severity of injury, as well as the protein adduct formation by reactive 1-NN metabolites. The antagonistic effects were primarily seen in the nasal transitional epithelium, which corresponds to the main site of histological changes attributed to ozone exposure (goblet cell metaplasia and hyperplasia). Long-term ozone exposure did not appear to alter susceptibility to 1-nitronaphthalene injury in other nasal regions. This study shows that long-term ozone exposure has a protective effect on the susceptibility of nasal transitional epithelium to subsequent 1-nitronaphthalene, a result which clearly contrasts with the synergistic toxicological effect observed in pulmonary airway epithelium in response to the same exposure regimen.