In this chapter, we have reviewed the immunopathology of LCMV disease and the possible mechanisms involved. While much of what has been learned about LCMV immunopathology is unique to this system, many of the basic principles can be used to increase our understanding of viral immunopathology in other systems. For example, knowledge of the immune mechanisms mediating LCMV hepatitis may provide insights into understanding and managing infections such as chronic active hepatitis B. Chronic active hepatitis B is likely immune mediated, given that the majority of chronic hepatitis B carriers do not have ongoing liver inflammation. As monoclonal antibody and cytokine immunotherapy becomes increasingly available, development of successful treatment modalities will depend upon a greater understanding of the effector arms of the immune system mediating hepatitis B liver damage. Immune-complex disease similar to that seen in LCMV carrier mice has been seen in other chronic viral infections. These include chronic hepatitis B, HIV, and lactate dehydrogenase virus in mice [13, 18, 44, 47, 54, 61]. Therapy of most immunecomplex disease has focused on treatment of the underlying disease or attending to the disease complications, such as end-stage nephritis. Studies of LCMV immunecomplex glomerulohephritis have shown that the disease severity varies depending on the genetic background of the host. Understanding the host factors involved in the development of immune-complex disease may provide insight into identifying those at risk and intervening prior to the development of the disease. Perhaps the most intriguing and challenging aspects of the study of LCMV immunopathology is its possible implications for better understanding infection with HIV. During HIV infection, as CD4 numbers decline, CD8+ CTL activity is lost and virus levels increase. As was seen during clearance of a chronic LCMV infection, the presence of CD4+ cells may be crucial in controlling viral spread through sustaining viral-specific CD8+ CTL activity. Infection of mice with the macrophage-tropic strain LCMV clone 13 results in immune suppression and susceptiblity to opportunistic infection with H. capsulatum. Studies of the mechanisms leading to susceptabilty to histoplasmosis may have implications for AIDS, since in endemic areas, disseminated histoplasmosis is a frequently seen complication in AIDS. Thus, studies of LCMV immunopathology serve to not only expand our knowledge of viral immunopathology in general, but also have practical implications for understanding and treating human disease.