C57BL and DBA/2, but not C57BL X DBA/2, marrow cells were rejected by non-immunized lethally irradiated C3H X C57BL mice. (C57BL X DBA/2)F1 X DBA/2 or X C57BL backcross mice were individually typed for H-2 and for growth of marrow cells in C3H X C57BL hosts. Each H-2b/H-2d graft proliferated while each H-2b/H-2b or H-2d/H-2d graft failed to grow. Thus, H-2 homozygosity of donor cells is one prerequisite for marrow allograft rejection. Various inbred strain or F1 hybrid marrow cells were infused into a series of irradiated hosts; success or failure of the grafts could not be correlated with homozygosity for known serologically detectable H-2 alloantigens. Thus, Hemopoietic histocompatibility (Hh) genes at the H-2 region determine antigens relevant for rejection by irradiated hosts. WB X DBA/2, WB X B10.D2, and WB X I were only H-2 heterozygous cells rejected. DBA/2, WB X DBA/2, and WB X B10.D2 cells grew in C57BL X DBA/2 hosts but were rejected by WB X C57BL mice, even though the donors were homozygous for a Hh specificity and both types of recipients were heterozygous for that same specificity. A mechanism for acceptance or rejection of Hh homozygous (parental) marrow cells by heterozygotes (F1 hybrids) is proposed which requires the existence of a closely linked “switch‘’ gene controlling expressivity of Hh specificities in the cis position only.