Delayed T-cell recovery is an important complication of allogeneic bone marrow transplantation (BMT). We demonstrate in murine models that donor BM-derived T cells display increased apoptosis in recipients of allogeneic BMT with or without GVHD. Although this apoptosis was associated with a loss of Bcl-2 and Bcl-X_L expression, allogeneic recipients of donor BM deficient in Fas-, tumor necrosis factor–related apoptosis-inducing ligand (TRAIL)- or Bax-, or BM-overexpressing Bcl-2 or Akt showed no decrease in apoptosis of peripheral donor-derived T cells. CD44 expression was associated with an increased percentage of BM-derived apoptotic CD4⁺ and CD8⁺ T cells. Transplantation of RAG-2-eGFP–transgenic BM revealed that proliferating eGFP^loCD44^hi donor BM-derived mature T cells were more likely to undergo to apoptosis than nondivided eGFP^hiCD44^lo recent thymic emigrants in the periphery. Finally, experiments using carboxyfluorescein succinimidyl ester–labeled T cells adoptively transferred into irradiated syngeneic hosts revealed that rapid spontaneous proliferation (as opposed to slow homeostatic proliferation) and acquisition of a CD44^hi phenotype was associated with increased apoptosis in T cells. We conclude that apoptosis of newly generated donor-derived peripheral T cells after an allogeneic BMT contributes to delayed T-cell reconstitution and is associated with CD44 expression and rapid spontaneous proliferation by donor BM-derived T cells.