Adherent bone marrow adult stem cells have been used in the treatment of GVHD. In this study, we investigate the capacity of a newly characterized population of stem cells, the Multipotent Adult Progenitor Cells (MAPC), to modulate acute GVHD. These cells were derived from bone marrow cells and grown extensively without evidence for replicative senescence or loss of differentiating capacity. MAPC significantly decreased mortality of acute GVHD. Moreover, they were non immunogenic and they were not sensitive to NK-lysis. When these cells were added to a mixed lymphocyte reaction (MLR), a dose-dependent suppression of T cell proliferation was observed that was non-MHC restricted, was reversible upon removal of MAPC from culture and was mediated by soluble factors. These data show that in vitro expanded adult stem cells can efficiently control an allo-reactive response associated with acute GVHD, that they are immuno-privileged and present strong immunosuppressive properties.