IL-1 is a pro-inflammatory cytokine consisted of two molecular species, IL-1alpha and IL-1beta, and the IL-1 receptor antagonist (IL-1Ra) is a natural inhibitor of both molecules. Although it is suggested that IL-1 potentiates immune responses mediated by T(h)2 cells, the role of IL-1 in asthma still remains unclear. In this study, we demonstrate that the ovalbumin (OVA)-induced airway hypersensitivity response (AHR) in IL-1alpha/beta-deficient (IL-1alpha/beta(-/-)) mice was significantly reduced from the levels seen in wild-type mice, whereas the responses seen in IL-1Ra(-/-) mice were profoundly exacerbated, suggesting that IL-1 is required for T(h)2 cell activation during AHR. OVA-specific T cell proliferation, IL-4 and IL-5 production by T cells, and IgG1 and IgE production by B cells in IL-1alpha/beta(-/-) mice were markedly reduced compared with these responses in wild-type mice; such responses were enhanced in IL-1Ra(-/-) mice. Using IL-1alpha(-/-) and IL-1beta(-/-) mice, we determined that both IL-1alpha and IL-1beta are involved in this reaction. Both IgG1 and IgE levels were reduced in IL-1beta(-/-) mice, while only IgE levels were affected in IL-1alpha(-/-) mice, indicating a functional difference between IL-1alpha and IL-1beta. These observations indicate that IL-1 plays important roles in the development of AHR.