Herpes simplex viruses 1 and 2 (HSV-I and HSV-2) invariably destroy the cells that they infect and in which they mUltiply. The destruction begins with the first stages of infection; the virus progressively parasitizes the machinery of the cell and even uses the host DNA as a source of deoxynucleotides for the replication of its own DNA. Yet the viruses are best known for their ability to remain latent in humans for the life of the host. In humans, infection with HSV-l typically occurs during the first six years of age as a consequence of exposure to an adult or child secreting virus. The disease, usually a mild stomatitis, is frequently undifferentiated from other diseases of childhood. In years to come, a large fraction of those infected exhibit recurrent lesions containing virus near the portal of entry, usually at the mucocutaneous junction of the lip. These recurrences are manifested in the face of a state of immunity indistinguishable from that of individuals who do not have recur rences. In the case of HSV-2, infection occurs either at birth or more commonly after the age of consent. The virus is transmitted by sexual contact, and initial lesions and recrudescences usually occur at or near genital organs but also occur in the mouth. While most studies of herpes simplex viruses center on the events of productive infections which invariably lead to cell death, the question that has attracted many investigators, including the au thors, into the field, is: How does a virulent virus, which is capable of massive destruction of the cells it infects, stay latent in humans for life without multiplying or destroying the cells in which it resides? HSV latency is not a novel discovery. It has been the subject of speculative and experimental publications since at least 1905 (20). The puzzle presented by HSV stemmed from the observations that the recurrences and underlying latency could be transmitted from person to person by inoculation of fluid from the vesicles of lesions, but virus could not be isolated from the sites of recurrent lesions in the interim between recrudescences (2, 30, 101, 107). The failure, also, to reproduce latent infection in its exquisite detail in isolated cells in culture seemed to suggest that HSV latency is very different con ceptually and mechanistically from phage lysogeny. Indeed, the early litera ture on HSV latency contains numerous explanations, and many of them seem to have been supported by the experimental evidence and models of the day. Doerr, reviewing the literature in 1938, stated:" All of these observations converge to indicate that the agent of herpes is no infectious agent which is conserved in the site of infection, but that it originates in the human organism, that is, endogenously."(23).