Human polioviruses are categorized into three distinct serotypes (types 1, 2, and 3) based upon their reactivity with specific antibodies. Although a great deal of information has been amassed about the induction and characterization of poliovirus antibody responses, little is known about cell-mediated immunity to poliovirus and its role in protection. Here, we show that intracutaneous injection of ultraviolet light-inactivated poliovirus into the tailbase of BALB/c mice induces delayed hypersensitivity (DTH) and T-cell proliferative (Tprlf) responses. Both DTH and Tprlf responses to poliovirus are mediated by Ly-1high2-, L3T4-bearing T cells. Moreover, known serologic cross-reactivity (i.e., antibody-mediated) of poliovirus serotypes is not predictive of cross-reactivity between the cell-mediated immune responses.