Background: This study looked at respiratory symptoms, peak expiratory flow rates (PEFRs), airway responsiveness to methacholine and inflammatory changes on bronchial biopsies, bronchial lavage (BL), and bronchoalveolar lavage (BAL) during natural antigenic exposure in nine subjects with pollen-sensitized seasonal asthma. Methods: The subjects recorded daily symptoms of asthma,cough and rhinitis, and morning and evening PEFRs between January and September, during and out of the pollen exposure. Baseline forced expiratory volume in 1 second, forced vital capacity, and methacholine responsiveness were measured every 3 to 4 weeks. BAL, BL, and bronchial biopsies were performed in the pollen season at the initial increase of asthma symptoms and out of pollen exposure. Results: At the time of bronchoscopy during the pollen season compared with out of season, asthmatic subjects had an increase in asthma symptom score (1.18 +/- 0.24/0.44 +/- 0.18, p < 0.05), a reduction of PEFR (407 +/- 23/442 +/- 20 L/min, p = 0.02), and a decrease in PC20 (1.15/1.48 mg/ml, p = 0.05). In asthmatic subjects, median BAL and BL cell counts and cell differentials during or out of antigenic exposure were similar, but BAL and BL eosinophils and metachromatic cells counts were always higher than in healthy subjects. In comparison with controls, biopsies obtained in asthmatic subjects showed airway lesions such as epithelial desquamation, squamous cell metaplasia, thickening of basal membrane, inflammatory cells (p < 0.05 for neutrophils), edema, and ciliary abnormalities. During pollen exposure, inflammatory signs increased, but this change was only significant for the extent of epithelial desquamation and neutrophil counts. No significant correlation was found between the intensity of airway inflammation and changes in airway responsiveness. Conclusions: In subjects with mild allergic asthma and pollen-induced asthma, seasonal antigenic exposure was associated with an increase in epithelial shedding and in the number of neutrophils on bronchial biopsies, suggesting a mild increase in baseline airway inflammation. However, these changes were not correlated with increases in airway responsiveness.