Upper respiratory tract viral infections have been reported in clinical studies to serve as risk factors for allergic sensitization. In order to study the relationship linking influenza virus illnesses to development of allergy, murine models of allergen sensitization were previously employed. These models showed that lethal influenza viruses were able to trigger allergen-specific immunoglobulin E (IgE) production and to inhibit tolerance to repeated exposure to aerosolized allergen in the mouse. The disadvantage of these murine models consists in the utilization of virulant and lethal strains of influenza virus. A nonlethal rat-adapted influenza virus (RAIV) host resistance model has been developed in our laboratory. It was used to evaluate the effect of influenza virus infection on IgE responses to inhaled ovalbumin (OA) in the rat. The high IgE-responder Brown-Norway (BN) rat was chosen for further study after comparing the IgE response to OA in Fischer 344 (F344) and BN rats. On d 1, BN rats were sensitized by administration of 1 mg OA subcutaneously alone or together with aluminum hydroxide (200 mg) and Bordetella pertussis (15 x 10(9) killed bacilli per rat in 1 ml), or only received saline. Rats were either infected with RAIV or sham-infected on d 0 (24 h prior to sensitization) or on d 15, 17, or 57. Rats were exposed for 3 min to aerosolized OA (OA 3% in phosphate-buffered saline) every week, starting on d 18. Serum OA-specific IgE was evaluated by reverse enzyme-linked immunosorbent assay (ELISA) 3 d after each OA challenge. BN rats elicited a detectable OA-specific IgE response that decreased after repeated aerosol exposures. Influenza virus infection transiently increased the OA-specific IgE response when rats were immunized with OA alone and were infected 1 d prior to the first challenge and also when rats received only saline on d 1, were exposed each week to aerosolized OA, and were infected prior to the seventh challenge. These results, with data previously reported in mice, emphasize the importance of upper respiratory tract viral infection in increasing IgE responses to allergens and may be of importance in human disease.