Background: Steroid-resistant asthma develops after adenoviral bronchiolitis. Objective: We sought to determine the effect of steroids on allergic lung inflammation in the presence of latent adenoviral infection. Methods: Guinea pigs with latent adenoviral (n = 12) or sham (n = 12) infections were sensitized and challenged with ovalbumin (OA) or sham sensitized and challenged with saline solution. The effect of steroids (20 mg/kg administered intraperitoneally) on OA-induced lung inflammation was examined by using quantitative histology as the outcome measure. Results: Latent adenoviral infection increased CD8⁺ cells in the airway wall and CD8⁺ cells, macrophages, B cells, and CD4⁺ cells in the lung parenchyma. Ovalbumin challenge, on the other hand, increased eosinophils, macrophages, B cells, and CD4⁺ cells in both the airway wall and lung parenchyma independent of the effect of latent adenoviral infection. In the sham-infected groups steroid treatment caused the expected reduction in the eosinophilic infiltrate induced by OA challenge in the airways without affecting the other cells. In the presence of both latent adenoviral infection and OA challenge, steroid treatment had no effect on allergen-induced eosinophilia but reduced CD8⁺ cells in the airways and CD8⁺ cells, CD4⁺ cells, and B cells in the parenchyma. Conclusion: Latent adenoviral infection and OA challenge result in different types of lung inflammation, and the presence of latent adenoviral infection causes OA-induced eosinophilic airway inflammation to become steroid resistant. (J Allergy Clin Immunol 2000;106:844-51.)