Transplantation of 5 x 10(5) DBA/2 (H-2(d)) bone marrow cells into irradiated B10 and 129-strain mice (both H-2(b)) resulted in graft failure in the first recipient strain and in graft take in the second. Transplantation of B10 (H-2(b)) cells into irradiated B10.BR and C3H mice (both H-2(k)) also resulted in failure in the congenic B10.BR recipients and take in the C3H mice. Resistance and susceptibility of B10 and 129-strain animals were specific for given H-2 alleles of donor cells. Transplantation of DBA/2 marrow into (B10 x 129)F(2) mice and of B10 marrow into (B10.BR x C3H)F(1) x C3H backcross mice revealed definite genetic control of the graft-rejection process, presumably at the level of alloantigen recognition. Resistance to allografts, or responder status, was conferred upon segregating mice by dominant alleles of two major independent autosomal loci. The effects of the loci were additive. Conversely, susceptibility to allografts, or nonresponder status, was due to the apparently recessive alleles of both loci. None of the genes was closely linked with the markers tf (tufted) and T (brachyury) of linkage group IX, A(w) (white-bellied agouti) of linkage group V, Sl (steel) of linkage group IV, and c(ch) (chinchilla) and p (pink eye, dilute) of linkage group I. There were suggestions, however, that the regulator genes of marrow graft rejection are either non-H-2 histocompatibility genes or other genetic factors closely linked with them.