We previously reported that the intratracheal instillation of diesel exhaust particles enhances allergic airway inflammation and hyperresponsiveness in mice. However, it is not known whether the effects of such instillation differ from those obtained with the daily inhalation of diesel exhaust. We therefore examined whether the inhalation of diesel exhaust would also enhance allergic reactions. Mice were exposed to diesel exhaust or clean air for 5 wk. After the first week, the animals were sensitized to ovalbumin by intraperitoneal injection. At the end of the exposure period, they underwent an ovalbumin challenge. Control animals received saline instead of ovalbumin. Independently of ovalbumin sensitization, diesel exhaust caused an increase in the numbers of neutrophils and macrophages in bronchoalveolar lavage fluid, whereas a significant increase in eosinophil numbers occurred only after antigen challenge combined with diesel exhaust exposure. Furthermore, ovalbumin alone caused an increase in eosinophil numbers in lung tissue, and this was enhanced by diesel exhaust. Exposure to diesel exhaust combined with ovalbumin sensitization, but not diesel exhaust inhalation alone, enhanced the number of goblet cells in lung tissue, respiratory resistance, production of ovalbumin-specific immunoglobulin E and G1 in the serum, and expression of interleukin-5 in lung tissue.