Mice sensitized and challenged with OVA were used to investigate the role of innate T cells in the development of allergic airway hyperresponsiveness (AHR). AHR, but not eosinophilic airway inflammation, was induced in T cell-deficient mice by small numbers of cotransferred gamma(delta) T cells and invariant NKT cells, whereas either cell type alone was not effective. Only V gamma 1(+)V delta 5(+) gamma delta T cells enhanced AHR. Surprisingly, OVA-specific alpha beta T cells were not required, revealing a pathway of AHR development mediated entirely by innate T cells. The data suggest that lymphocytic synergism, which is key to the Ag-specific adaptive immune response, is also intrinsic to T cell-dependent innate responses.