Herpes simplex genitalis (HSG) is an extremely common sexually transmitted disease for which there are no adequate control measures. The pathogenesis of HSV infections and the host-virus interactions which result in the development of recurrent disease remain incompletely understood. The proposed research is designed to investigate the possibility that differences among HSV strains, as determined by the techniques outlined below, can be correlated with different clinical manifestations of HSG. Virus strains from primary and recurrent disease will be compared as well as isolates from mild and severe recurrences. Close longitudinal follow-up of a stable patient population will permit sequential analysis of several isolates from the same individual. The proposed studies will employ techniques which evaluate both cellular and humoral aspects of host defense. Each isolate's ability to resist inactivation will be measured in a syngeneic system in which virus replication is inhibited by different combinations of host mononuclear cells and serum. Non-specific resistance to infection will be estimated by measuring the growth of different isolates in lymphocytes and macrophages obtained from patents' peripheral blood. The ability of the isolates to induce T-cell cytotoxicity in patients' circulating cells will be evaluated, as well as the ability of the isolates to both induce and inhibit lymphocyte blastogenesis. The susceptibility of the isolates to interferon will be measured, and antibody- and complement-dependent virus neutralization kinetic studies of the isolates will be performed. If we are able to correlate differences among HSV strains with different clinical manifestations of HSG, these studies may elucidate pathogenic factors which are related to unusually severe or frequent HSG recurrences.