Vpr, an accessory protein of HIV, is known to affect viral replication as well as cell growth, differentiation, and apoptosis in vitro. To investigate its pathogenicity in vivo, we have produced mice transgenic for the HIV-1 vpr gene with the CD4 enhancer/promoter. Interestingly, apoptotic death of T lymphocytes was enhanced in those mice, causing marked reduction of T cells in lymphatic organs and peripheral blood. Involvement of Bcl-x, Bax, and Caspase-1, but not of the Fas–Fas ligand system, was suggested in the apoptotic processes. These observations suggest that Vpr is involved in the pathogenesis of T cell depletion in HIV-infected people.