Inducible co-stimulator ligand (ICOSL) is a rather newly defined co-stimulatory molecule, which, through interaction with ICOS expressed on T cells, plays an important role in T-cell activation, differentiation and function. T(h)2-type immune responses are critical for the development and maintenance of allergic responses including asthma. Using knockout (KO) mice, we have assessed the role of ICOSL in allergic airway inflammation and responsiveness using a standard mouse asthma model induced by ovalbumin (OVA) sensitization and challenge. Our data show that OVA-treated ICOSL KO mice exhibit significantly less lung eosinophilic infiltration, histopathology, mucus production and virtually no airway hyperresponsiveness in contrast to wild-type (Wt) counterparts. Serum antibody analysis showed that antigen-specific IgG1, IgG2a and IgE titers in ICOSL KO mice were significantly lower than those of Wt controls. Also, CD4(+) T cells isolated from ICOSL KO mice produced less T(h)2 cytokines (IL-4, IL-5, IL-10 and IL-13) but more T(h)1 (IFN-γ) and IL-17 than their Wt controls. Taken together, we conclude that ICOSL plays an important role in predisposing individuals to allergic airway hyperresponsiveness by enhancing IgE antibody class switching and T(h)2 cytokine production and diminishing the T(h)17 response and airway eosinophilia.