Repeated low-dose allergen challenge increases airway hyperresponsiveness in atopic asthmatics. However, it is not known whether low-dose allergen challenge increases airway inflammation. Eight atopic asthmatics were enrolled in a controlled, cross-over study to evaluate the effect and time course of repeated low-dose allergen challenge on airway inflammation and hyperresponsiveness. The dose of allergen to reduce forced expiratory volume in one second (FEV1) by approximately 5% was selected in a screening allergen challenge. The subjects then were challenged for five consecutive days with either diluent or the selected low-dose of allergen. Methacholine airway hyperresponsiveness (PC20,meth) was measured and sputum induced on days 1, 3 and 5 of the repeated challenge, and then 1 day and 3 days after the last challenge. Repeated low-dose allergen challenge caused small reductions in FEV1, but increased airway eosinophils and interleukin (IL)-5, airway hyperresponsiveness, asthma symptoms and beta2-agonist use, all of which peaked on days 3 or 5 of the challenge. The mean (SEM) percentage sputum eosinophils was 21.2 (0.7)% after allergen versus 3.9 (0.1)% after diluent (p<0.001); percentage EG2+ cells were 13.4 (03)% after allergen versus 1.1 (0.04)% after diluent (p<0.01) and geometric mean (GSEM) eosinophil cationic protein (ECP) was 1061.8 (1.6) microg x L(-1) after allergen versus 447.03 (1.2) microg x L(-1) after diluent (p<0.05). Geometric mean (GSEM) IL-5 was 71.4 (1.4) pg x mL(-1) after allergen versus 18.4 (1.04) pg x mL(-1) after diluent (p<0.01). All the changes had resolved by 3 days after the last challenges. The study demonstrated that repeated inhalation of a low-dose of allergen causes airway eosinophilia and increases in interleukin-5, associated with airway hyperresponsiveness, and mild worsening of asthma control, without the development of marked acute bronchoconstriction or the development of late responses.