Inoculation of mice with herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) by the vaginal route resulted in viral shedding during the acute phase of the infection and the development of a latent infection in vaginouterine tissue lasting up to one year in greater than 25% of the animals. Immunization with either serotype of HSV markedly reduced viral shedding when animals were subsequently challenged with the homologous serotype, but immunization with HSV-2 was significantly less effective in preventing the development of a latent infection in the vaginouterine tissue after challenge than was immunization with HSV-1.