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The gradual depletion of CD4+T lymphocytes during the development of AIDS may be due, at least in part, to a process referred to as apoptosis. This process involves a Ca2+dependent nuclear endonuclease that cleaves the chromatin at internucleosomal junctions. In addition, we have recently provided evidence that apoptosis may be responsible not only for the progressive loss of CD4+T lymphocytes but may be operative in CD8+T lymphocytes as well. Here, we describe mechanisms which by direct and indirect pathways may induce apoptosis during HIV infection and thus leading to elimination of T cells.