The immunogenicity of a DNA free herpes simplex subunit vaccine was evaluated in chimpanzees and rabbits. The results clearly demonstrate that 1 injection of 3 micrograms/kg elicited antibodies as well as cell-mediated immunity in all the animals studied. These antibodies persisted for at least 6 months. Furthermore the vaccine also protected 50% of the animals against an experimental infection and reduced the rate of latent infection in nervous sensory ganglia.