Primary infections with herpes simplex virus type 2 (HSV-2) suppress the antibody response to secondary HSV-1 and -2 infections in the BALB/c mouse. In contrast, a challenge by the i.p. route using a vaccinia virus-HSV-1 glycoprotein B (VV gB1) recombinant induces a significant enhancement of the antibod response. This booster reaction is also observed if a challenge with a formalin-inactivated HSV-1 vaccine is performed. Although no or low humoral and vaginal antibodies are detectable after a single i.p. infection with the VV gB1 recombinant or the HSV-1 vaccine, protection against vaginal challenge with HSV-2 is induced. This points to the important role of cellular immunity for vaginal infections.