Apoptosis has been implicated in a variety of physiological processes ranging from tissue modeling to deletion of autoreactive T lymphocytes during thymic development. The recent finding that a large proportion of peripheral T cells from HIV-infected subjects (corrected from subjects) apoptose in culture raises an important issue: does this represent a pathologic mechanism by which the virus disrupts the immune system, or a normal physiologic response to virus-mediated T-cell loss? To study the potential relationship between apoptosis and lymphopoiesis, we compared apoptosis rates in unstimulated lymphocyte cultures from healthy subjects, HIV+ gay men, and bone marrow transplant (BMT) recipients undergoing immune reconstruction. BMT recipients were chosen because they undergo massive regeneration of lymphocytes following marrow ablation and graft infusion. The data obtained in BMT recipients suggests that elevated apoptosis accompanies, and is the consequence of, elevated lymphopoiesis. We also found a strong inverse relationship between in vitro T-cell apoptosis rates and peripheral T-cell counts. These results provide new interpretation for elevated apoptosis observed in HIV-infected individuals--that it reflects increased T-cell turnover consequent to virus-mediated destruction of CD4+ T-cells.