To elucidate the role of eosinophils, neutrophils and lymphocytes for the development of bronchial hyperresponsiveness (BHR) following antigen exposure, we have developed a guinea pig model of BHR. Guinea pigs immunized by repeated exposure to aerosolized ovalbumin (OA) were intravenously given metopirone, a cortisol synthesis inhibitor, 24 hrs before and 30 min before antigen challenge, and to prevent death from immediate severe bronchoconstriction, chlorpheniramine maleate was also injected. After antigen challenge with high dose of OA, LAR occurred in twelve of fifteen animals (80%) and the bronchial responsiveness to acetylcholine (Ach) was significantly increased. Histologic examination at 72 h showed a significant increase in the number of eosinophils but not neutrophils within the tracheal walls. However, there was no significant correlation between the change in bronchial responsiveness to Ach at 24 h and the number of eosinophil in the tracheal wall at 72 h. When guinea pigs were treated with Cyclosporin A or FK506, T-lymphocyte selective immunosuppressive agents, from the beginning of immunization period, both eosinophil infiltration and an increase in bronchial responsiveness were inhibited. These results suggest that eosinophils and T-lymphocytes may play an important role in the development of bronchial hyperresponsiveness.