The mechanisms underlying the development of airway hyperresponsiveness are not fully delineated. We addressed this question by studying the effects of passive sensitization with anti-OVA IgE on the development of altered airway responsiveness (AR) following local challenge with OVA in normal and athymic mice. Both normal and athymic BALB/c mice developed allergen-specific immediate cutaneous hypersensitivity after passive sensitization with anti-OVA IgE. In contrast, the combination of local challenge with allergen via the airways and passive sensitization triggered the development of airway hyperresponsiveness only in normal but not in athymic mice. Treatment of athymic mice with IL-5 significantly increased eosinophil accumulation in the lungs after local challenge with OVA; increased airway reactivity was only observed in athymic mice which received anti-OVA IgE, not an unrelated IgE, plus IL-5 treatment and airway challenge with OVA. These findings identify the requirement for allergen-specific IgE and IL-5 for the development of airway hyperresponsiveness following allergen challenge via the airways.