Natural killer cells can weakly resist engraftment of allogeneic bone marrow transplants in mice. Functional studies suggest that natural killer cell tolerance can be induced by bone marrow transplantation. Human natural killer cell inhibitory receptor repertoires differ between individuals, depending on their MHC genotype. This supports the concept that the human natural killer cell repertoire, like that of mice, adapts to the MHC molecules presented in its environment. Natural killer cells play a greater role in rejecting xenogeneic than allogeneic bone marrow and have been implicated in the rejection of xenogeneic solid organ transplants. Natural killer cell inhibitory receptors may have a lower likelihood of cross-reacting with xenogeneic than with allogeneic MHC class I molecules; important glycosylation differences between species may affect the propensity of natural killer cells to kill xenogeneic targets.