Mice depleted of gammadelta T cells by in vivo administration of anti-TCRgammadelta monoclonal antibodies showed susceptibility against an intravaginal infection with herpes simplex virus type 2 (HSV-2). The systemic Th1 response was impaired in the gammadelta T-cell-depleted mice. Mice deficient in the Vdelta1 T subset were susceptible to an intravaginal infection with HSV-2. Intraepithelial gammadelta T cells bearing Vdelta1 may help protect against intravaginal infection with HSV-2 through promoting the systemic Th1 response.