Nitrogen dioxide exposure-induced mucosal pathology of the guinea pig trachea was studied. Exposure to 3 or 9 ppm of nitrogen dioxide for 6 h a day, 6 times weekly for 2 weeks resulted in decreased ciliary activity as well as a dramatic eosinophil accumulation to the epithelium and submucosal layer. Especially exposure to 9 ppm of nitrogen dioxide induced epithelial injury through the activation of eosinophils accumulated in the tracheal mucosa. The epithelial damage induced by nitrogen dioxide could lead to hyperresponsiveness and prolonged allergic inflammation. Our study suggests that environmental nitrogen dioxide could contribute to the hyperresponsiveness and could most probably be involved in the development and chronicity of airway allergic disorders.