The quantitative depletion of T-cells has long been established as a highly effective way to prevent graft-versus-host disease. The disadvantages associated with T-cell depletion (TCD), including loss of the graft-versus-leukemia effect and impaired immune recovery have been important drawbacks for application on a wider scale. Recently, however, new approaches such as the use of peripheral blood stem cells and the application of TCD, in conjunction with delayed donor lymphocyte infusion, have opened new possibilities. The first clinical studies addressing the merits of these approaches suggest that effective prevention of graft-versus-host disease may be achieved by TCD, whereas the graft-versus-leukemia effect may be maintained by delayed donor lymphocyte infusion. Also, immune recovery may be accelerated by the use of peripheral blood stem cells. New techniques to manipulate stem cell grafts in vitro are being developed with the purpose to either selectively delete alloantigen specific T cells or tolerize such T cells by blocking costimulatory pathways. As a result, the in vitro manipulation of T cells of allogeneic stem cell grafts currently enjoys renewed scientific interest. (C) 2000 Lippincott Williams and Wilkins, Inc.