Immune hypersensitivity to house dust mite antigen (HDM) is a frequent cause of respiratory allergy. The objective of this study was to determine whether exposure to NO2, a common indoor air pollutant, modulates immune responses to HDM and influences immune-mediated lung disease. Brown Norway rats were immunized ip with 100 micrograms semipurified antigen and Bordetella pertussis adjuvant and challenged 2 weeks later with an intratracheal injection of 50 micrograms of a crude antigen preparation. Exposure to 5 ppm NO2 for 3 hr after both immunization and challenge procedures resulted in significantly higher levels of antigen-specific serum IgE, local IgA, IgG, and IgE antibody than air controls, and increased numbers of inflammatory cells in the lungs. Lymphocyte responsiveness to antigen in the spleen and MLN was also significantly higher in NO2-exposed animals. These data show that exposure to a common air pollutant can upregulate specific immune responses and subsequent immune-mediated pulmonary inflammation.