In order to examine the dose-dependence of the airway response to animal allergens we performed environmental challenges on 17 workers with documented IgE-mediated allergic reactions to laboratory rats. The 1-h environmental challenges were conducted in a vivarium during cage cleaning (high-allergen challenge), quiet sitting (low-allergen challenge), or in a remote location (sham challenge). During the high antigen conditions, mean Rat n 1 concentration was 166 +/- 28 ng/m3 compared with 9.6 +/- 3 ng/m3 in the low-allergen conditions. Nasal symptoms and nasal lavage mediator concentrations were significantly lower during the low-allergen conditions, but the pulmonary response was similar in terms of symptom scores, coughs, or FEV1 change. Using covariate analysis to examine the interaction of airborne allergen concentration, IgE-mediated sensitivity, and airway hyperresponsiveness, it could be shown that both upper and lower airway responses were strongly dependent on airborne allergen concentration but not on the degree of IgE sensitivity to rat allergen. We concluded that within sensitized workers, acute airway response is determined almost entirely by the intensity of environmental allergen exposure and the degree of bronchial hyperresponsiveness but not by the degree of IgE-mediated sensitivity.