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Although the major cellular target of HIV is the CD4 lymphocyte, the virus has been shown to infect numerous other cells of the immune system including macrophages, dendritic cells and CD8 lymphocytes. In vivo it is likely that infection of CD8 lymphocytes with HIV occurs at times when CD4 is expressed on the cell surface. This occurs during CD8 lymphocyte development in the thymus and during activation in the periphery. Evidence supporting infection in the thymus comes from post-mortem examination of thymic tissue from HIV infected patients and from experimental infection of thymocytes in the Thy-hu mouse model. Support for infection during activation is provided by the observation that a greater proportion of activated than non-activated CD8 lymphocytes carry the HIV provirus.