The guinea pig model of genital herpes has proved useful for the evaluation of experimental herpes simplex virus vaccines. The model shares many of the features of genital herpes in humans, including a natural route of inoculation that results in self-limiting primary vulvovaginitis. Latent infection is established in sensory ganglia, and animals experience both spontaneous and ultraviolet radiation-induced recurrence of infection. Many humoral, cellular, and cytokine responses to herpes simplex virus type 2 infection in the guinea pig have been characterized. Both inactivated subunit immunogens and live, attenuated virus have been shown to afford some protection against primary disease, although they generally do not prevent acute viral replication or the establishment of latency. Because latently infected guinea pigs experience recurrent infections, this model has been used to explore immunotherapeutic approaches to the control of recurrent disease. With the development of more defined immunologic reagents, this model should prove useful for exploring the immune responses that are important in the control of primary, latent, and recurrent herpes simplex virus type 2 infections.