We have studied the development of airway hyperresponsiveness and the pulmonary cell infiltration in a guinea-pig model in which both initial sensitization and subsequent exposure to the antigen were performed by aerosol. Enhanced bronchopulmonary response to aerosol administration of acetylcholine (ACh) and 5-hydroxytryptamine (5-HT) was observed 3–4 hr and 18–24 hr after antigen exposure of sensitized animals. In contrast, when ACh and 5-HT were administered intravenously 3–4 hr after the challenge, no significant alteration of the dose -response curves was observed. However, 18–24 hr after antigen challenge, a marked leftward shift of the dose-response curve was observed on intravenous injection of ACh or 5-HT. The increased bronchial reactivity to aerosoli?.ed ACh in sensitized and challenged guinea-pigs reached a maximum by days 2–4, was still significantly increased at day 5 and returned to the basal value by day 8. No further alteration of the dose-related bronchopulmonary response to aerosol or intravenous administration of ACh was recorded 24 hr after a second antigen challenge, performed 8 days after the initial one. The analysis of bronchoalveolar lavage fluids showed a significant increase in the number of polymorphonuclear neutrophils 3–4 hr after the exposure of sensitized animals to the antigen, which was also associated with a significant eosinophilia at 18–24 hr. Histological examination of lung specimens obtained from animals 3–4 hr following challenge demonstrated eosinophil infiltration in the peribronchial regions and bronchial walls, as well as within the epithelium. Furthermore, as compared to time 3–4 hr, less eosinophils in the peribronchial area and submucosa were counted 24 hr after antigen challenge. However, a role of eosinophil-derived products in the development of bronchial hyperresponsivenss in this experimental model remains to be established.