T cells regulate airway reactivity but their role in ozone (O₃)-induced airway hyperresponsiveness (AHR) is not known. Different strains of mice including those that were genetically-manipulated or antibody-depleted to render them deficient in total T cells or specific subsets of T cells were exposed to 2.0 ppm of O₃ for 3 hrs. Exposure of C57BL/6 mice to O₃ resulted in a transient increase in airway reactivity, neutrophilia, and increased numbers of epithelial cells in the lavage fluid. TCR--/- mice did not develop airway hyperresponsiveness, although they exhibited an increase in neutrophils and epithelial cells in the lavage fluid. Similarly, depletion of T cells in wild-type mice suppressed O₃-induced airway hyperresponsiveness without influencing airway inflammation or epithelial damage. Depletion of V1+, but not of V4+ T cells, reduced O₃-induced airway hyperresponsiveness and transfer of total T cells or V1+ T cells to TCR--/- mice restored airway hyperresponsiveness. Following transfer of V1+ cells to TCR--/- mice, restoration of airway hyperresponsiveness after O₃ exposure was blocked by anti-TNF-. However, airway hyperresponsiveness could be restored in TCR--/-mice by transfer of T cells from TNF--deficient mice indicating another cell type was the source of TNF-. These results demonstrate that TNF- and activation of V1+ T cells are required for the development of airway hyperresponsiveness after O₃ exposure.