Recently, cases have been reported in which a mixed chimeric state of blood cells is established after liver transplantation. Because the established chimerism may have aided in the induction of donor-specific tolerance, the mechanism responsible for this chimerism is of clinical importance. To establish this, we examined cells in adult mouse liver and identified the presence of c-kit+ Sca-1+ Lin(lo/-) cells. These cells were capable of forming in vivo as well as in vitro colonies. Furthermore, the cells could reconstitute bone marrow of lethally irradiated recipient mice for at least 12 months. These data obtained from the mouse study strongly suggest that hematopoietic stem cells residing in the donor liver are responsible for mixed chimerism and maintenance of tolerance after liver transplantation.