Effective vaccines against genital herpes simplex virus type 2 (HSV-2) may need to induce genital tract immune responses. To determine local antibody responses to HSV-2 glycoproteins gB2 and gD2 in an intramuscular subunit vaccine, cervical secretions from HSV-seronegative women and HSV-1-seropositive women were tested for IgG and IgA to gB2 and gD2 by enhanced chemiluminescence Western blot. Most (94%) of the seronegative subjects developed cervical IgG to gB2, IgG to gD2, and IgA to gB2; 72% developed IgA to gD2. All HSV-1-seropositive subjects had cervical IgG responses to vaccine gB2 and gD2, 85% had IgA responses to gB2, and 50% had IgA responses to gD2. Responses were more rapid and titers more consistently sustained in the HSV-1-seropositive women. Further, vaccination resulted in cervical IgG and IgA titers comparable to those to HSV-2 gB2 and gD2 in response to recurrent HSV-2 genital infection.