In man and experimental animals the evidence strongly indicates that inflammation plays a significant role in the resistance to and in the recovery from viral infections. Once a virus gains entry, the host's polymorphonuclear leukocytes (PML), macrophages, and lymphocytes respond, attempting to eradicate the invading pathogen and to prevent the spread of the virus. The role various types of inflammatory cells play in vivo is presently unclear. Leukocytes may facilitate recovery by phagocytosing and killing virus particles, lysing infected cells, and preventing the spread of virus from cell-to-contiguous cell. Each of these functions can be examined in tissue culture. Using these techniques we propose to define the role of various types of inflammatory cells in an effort to understand the cellular response to in vivo infections. We hypothesize that the reason man and certain strains of mice have recurrent and sometimes lethal viral infections is because their leukocytes are incapable of containing them. Herpes simplex virus (HSV) is the virus we intend to study because it spreads by each of the routes by which viruses are known to spread (i.e., extracellularly, from cell to contiguous cell, and to daughter cells in mitosis). PML, macrophages, and lymphocytes will be isolated from three separate patient populations: 1) Those who have never had herpetic infections, 2) individuals with infrequent disease and 3) subjects with multiple, frequent recurrent infections. In addition the leukocytes from HSV-resistant and susceptible inbred mouse strains will be assessed for the antiviral activity of their leukocytes. In quantitative assay systems we shall determine how effective the various human and murine leukocytes are in containing virus infections in vitro. Having assayed the antiviral activity of the various types of leukocytes we shall be able to detect which leukocytes are dysfunctional and to what extent they are incapable of containing the infection. Our ultimate goal is to develop in vitro tests for detecting susceptible states in man and to develop a basis by which we might therapeutically reverse the susceptibility of the patient and thereby protect him from infection.