Genital herpes is different from other common venereal diseases in that there is no cure. As yet the natural history of genital herpes is not well understood. There are many unanswered questions regarding the biology of the disease; the virulence of the virus strains, individual host responses, and means for prevention and control all require further investigation. The study of genital herpes has been greatly aided in recent years by the development of animal models. The clinical and pathologic features of acute and recurrent genital disease of guinea pigs inoculated with low doses of herpes simplex virus are similar to those seen in human infection. Therefore, questions not readily studied in human infection--such as latent infection in the nervous system, the natural history, prevention, and treatment of neonatal herpes, the effects of immunosuppression on herpes infection, and the efficacy and toxicity of antiviral drugs and vaccines--are amenable to study in the guinea pig model. The applications of this animal model and its relevance to human disease are herein reviewed.