IL-21R signaling is required for the development of Th2-driven allergic airway inflammation. BALB/c and IL-21R–deficient mice were immunized intraperitoneally with OVA protein adsorbed in alum adjuvant, followed 10 days later by intranasal challenge with OVA on 4 consecutive days. Two days after the final intranasal challenge (A) The number of eosinophils, lymphocytes, and macrophages that had infiltrated into the airways was determined by BAL and differential cell counts; (B) lung draining lymph nodes were removed and total lymph node cells cultured in the presence of OVA protein for 72 hours. [³H] thymidine incorporation over the last 12 hours of culture was measured as an indicator of cell proliferation. (C) One day after intranasal challenge, mice were exposed to increasing concentrations of acetyl-β-methacholine-chloride (MetCh) and airway hyperresponsiveness was determined using a full-body unrestrained plethysmograph. (D) OVA-specific IgG1, (E) IgA, and (F) total IgE were measured in BAL fluid. Data show averages ± SD of a representative experiment using 4 to 7 mice per group. Similar results were obtained in 3 independent experiments.