Immune cells expressing both NK and T cell markers include CD1d-dependent NKT cells and CD1d-independent NKT-like cells. We now describe the presence of NK1.1(+)CD8(+) T cells in the liver, but not other tissues (spleen, bone marrow, thymus or peripheral blood) in mice receiving allogeneic hematopoietic cell transplantation (allo-HCT). These cells are CD1d-independent TCRαβ(+) T cells with an effector/memory CD44(hi)CD62L(-) phenotype, and do not express Ly49 receptors. Furthermore, these cells were derived from donor splenocytes, but not bone marrow cells. Depletion of CD8(+), but not NK1.1(+), cells from donor splenocytes prior to transplantation prevented the generation of NK1.1(+)CD8(+) T cells, indicating that these cells arose from donor NK1.1(-)CD8(+) splenic T cells. These results provide direct evidence that donor CD8(+) T cells can acquire NK1.1 expression upon activation in allo-HCT recipients and that these NK1.1(+)CD8(+) NKT-like cells maintain an effector/memory phenotype and persist in the recipients with preferential localization in the liver