Telomeres are complex protein-DNA structures located at the ends of eukaryotic chromosomes. In a normal cell, telomere DNA shortens with cell divisions. Such a telomere loss may act as a mitotic clock to eventually signal cell cycling exit and cellular senescence. In a transversal study, we found a marked decrease in telomere length of peripheral blood mononuclear cells in HIV-infected patients with advanced immunodeficiency. This telomere reduction concerns T4, T8, and B lymphocytes, providing evidence of high turnover of these cells in the course of HIV infection. These data suggest that replicative senescence could be involved in the final immunosuppression and may have important therapeutical implications.