Acute rejection of allogeneic and semiallogeneic marrow grafts has long been considered to be a function of the natural immune system because it shares many features with NK activity in mice. With the use of a recently developed in vivo adoptive transfer assay in which spleen cells are transferred from mice able to reject a particular marrow graft into mice that fail to do so, we show that the cells responsible for induction of marrow graft rejection indeed display the phenotype of NK cells: they lack the T cell Ag CD4 and CD8 but express the NK Ag NK1 and ASGM1. The rejection induced by adoptively transferred cells is exquisitely specific--a feature that points to a specific recognition process by the transferred cells. To elucidate what the recognition structure on these cells may be we found that they express CD3 and most likely the beta-chain of the TCR. Highly purified responder cells with the NK1+, CD3+, CD4-, CD8- phenotype, when transferred into nonresponder recipients, cause specific marrow graft rejection. We conclude that the acute rejection of bone marrow grafts is caused by a cell that expresses NK phenotype but is of T cell lineage. This may suggest the specificity of acute marrow graft rejection is caused by a specific recognition process that involves TCR.