Genital HSV infections and their complications continue to be epidemic. HSV-2 antibodies are found in 20% of the general U.S. population and in over 50% in many patient populations. More than 2/3 of HSV-2 seropositive persons have subclinical infection, i.e, are asymptomatic or have unrecognized symptomatic disease. Little is known, however, about the natural history or immunobiology of asymptomatic genital herpes. Recent studies suggest the frequency of reactivation, the number of anatomic sites infected, and host immune responses differ between patients with symptomatic vs asymptomatic genital herpes. Project I describes several prospective studies directed at defining the frequency and epidemiologic correlates of persons with true asymptomatic as compared to those with unrecognized symptomatic disease. Studies are proposed to define the frequency of asymptomatic shedding in the male and female genitourinary tract. The role asymptomatic vs symptomatic carriers play in transmission will be evaluated. Project II continues ongoing work defining the perinatal morbidity of asymptomatic genital herpes. Pilot studies indicate first episode genital HSV infections in the pregnant mother are associated with a disproportionately large share of the cases of neonatal herpes. Anatomic sites of shedding, viral type and the use of fetal scalp electrodes may also influence the efficiency of transmission of HSV to the neonate. Studies are proposed to further define factors associated with asymptomatic shedding at delivery and efficiency of transmission to the neonate. Project III is directed at expanding upon recent data showing a closer correlation between asymptomatic cervical reactivation of HSV and local as compared to systemic immune responses. Newly developed sensitive quantitative immunoassays to HSV proteins will assess whether local antibody responses vary with asymptomatic reactivation.