Hybrid resistance to parental H-2b bone marrow grafts is directed to a cell surface structure controlled by the Hh-1 locus in or near the H-2D region. The nature of this surface structure is not known. Since homozygosity at the class I H-2D locus or loci in this haplotype would seem a necessary but not sufficient condition for the grafts' susceptibility to resistance, we tested whether the expression of this phenotype is dependent on the expression of class I H-2Db determinants. Cloned variants of H-2b tumor RBL-5 were obtained by immunoselection for the absence of H-2Db expression, as determined by the inability to bind specific antibody and to induce or react with alloreactive cytotoxic T lymphocytes. The three clones used in this study were H-2Db negative but H-2Kb positive and were natural killer cell resistant. When tested in vivo as competitive inhibitors the variant cells were capable of blocking hybrid resistance to parental H-2b bone marrow grafts as were unselected H-2Db-positive parental line cells. Therefore, H-2Db expression is irrelevant for Hh-1b expression. An incidental observation was that YAC-1 cells, a non-H-2b tumor with pronounced susceptibility to natural killing, were able to block hybrid resistance. This reactivity, not observed in our previous studies, raises the possibility that at least some of the effector cells are cross-reactive or capable of dual recognition.