Human peripheral blood mononuclear cells from 15 normal, healthy adult volunteers proliferated in vitro against a panel of enteroviral antigens, including coxsackievirus B3, coxsackievirus B2, coxsackievirus B6, coxsackievirus A16, and poliovirus 1. No proliferation against the cardiovirus encephalomyocarditis virus occurred. Lymphocytes obtained from cord blood drawn from seven neonates were uniformly nonresponsive to enteroviral antigens. Although serum neutralization antibody titers indicated different exposure histories of the volunteers, only one had a titer against coxsackievirus B6, a rare isolate in the United States. The peripheral blood mononuclear cells from each volunteer responded in vitro to each enterovirus tested even though not all individuals had serum neutralizing antibody against each virus. The predominant cell type responding in vitro was the CD4+ T cell. Denaturation of viral antigen by Formalin did not prevent the recognition of the common group antigen by the T cells, indicating that noninfectious virus can also serve as antigen. These data demonstrate that human T cells recognize a common enterovirus group antigen(s).