Heavily irradiated mice of several inbred and F1 hybrid strains were classified as resistant or susceptible to allogeneic or parental grafts of 106 NZB bone marrow cells depending on the 5-day hemopoietic repopulation of host spleens. Several strains did not support the growth of donor cells despite the total-body irradiation. NZW × NZB F1 mice resisted the growth of as many as 4 × 107 parental cells, the strongest barrier ever observed in mice for marrow transplants. The failures of growth were due to host-anti-graft reactions depressible by pretreatment of recipients with cyclophosphamide or horse anti-mouse thymocyte serum. Analysis of the progeny of two separate backcrosses of F1 mice to NZB indicated that two non-linked autosomal genes controlled resistance. One of these genes was in linkage group IX, 31.42 crossing-over units away from the D end of H-2, specifying or controlling the expression of alloantigen-like components of hemopoietic cells (Hh-gene). The second gene had an epistatic effect, probably by regulating the recognition of, or the reactivity to, Hh-gene products.