IRRADIATED MHC-heterozygous mice often reject bone marrow cells transplanted from one of the homozygous parental strains, a phenomenon ('hybrid resistance') that appears to violate the laws of transplantation^1,2. Rejection of parental and allogeneic marrow cells also differs from conventional T cell-mediated rejection mechanisms as it is effected by NK1.1⁺cells^3–5. To account for the unusual specificity of bone marrow rejection, it has been proposed that NK1.1⁺ cells destroy marrow cells that fail to express the full complement of self MHC class I (MHC-I) molecules⁵. We show here that NK1.1⁺ cells in normal mice reject haemopoietic transplants from mice that are deficient for normal cell-surface MHC-I expression because of a targeted mutation in the β₂-microglobulin gene^6–9. These findings demonstrate that deficient expression of MHC-I molecules renders marrow cells susceptible to rejection.