In order to investigate the role of interleukin-5 (IL-5) in airway hyperreactivity and eosinophilia, we observed the effect of inhaled recombinant human IL-5 on airway responsiveness to methacholine and cell populations in induced sputum in eight patients with allergic bronchial asthma using a placebo-controlled study design. Our results demonstrated that the inhalation of IL-5 did not alter lung function in allergic asthmatics. In the control experiments receiving either vehicle or 0.4 ng of endotoxin, methacholine PC20 values did not change nor did the numbers of eosinophils or eosinophil cationic protein (ECP) sputum values change from baseline. In contrast, after IL-5 inhalation, methacholine PC20 fell from baseline (0.90 +/- 166 mg/ml) to 0.32 +/- 1.63 mg/ml (p < 0.01) at 24 h, and to 0.55 +/- 1.49 mg/ml (p < 0.05) at 48 h. Accompanying this increased airway sensitivity was a significant eosinophilia and elevated concentrations of ECP in induced sputum. Our data provided direct evidence that IL-5 increases airway responsiveness and infiltration of activated eosinophils into the airway in patients with allergic bronchial asthma. It also could be concluded that the observed airway hyperreactivity and eosinophilia were not endotoxin related.