The Hh-1 (hybrid histocompatibility) effect in which F1 hybrids with heterozygosity at the "D end" of the H-2 complex can reject parental grafts of the H-2b haplotype was examined in four H-2 mutants wherein the mutation had affected the H-2Db, H-2Dd, or H-2Ld genes. In bone marrow grafting experiments it was shown that two separate mutations affecting the H-2Db locus did not affect the Hh-1 gene, suggesting that H-2Db and Hh-1 are probably two different genes. By contrast, experiments with two mutants, one affecting the H-2Dd and H-2Ld loci (B10.D2-H-2dm1) and the other a loss mutation at the H-2Ld locus (BALB/c-H-2dm2), demonstrate an alteration in the hybrid histocompatibility phenomenon and the presumption is made that the Hh-1 and H-2Ld locus are identical. This presumption was supported by studies of Hh-1 using the EL4 tumor grafting model where marked differences in growth were noted in the (B10 X BALB/c)F1 and (B10 X BALB/c-H-2dm2)F1 hybrids. By contrast, the functionally related natural killer (NK) phenomenon appeared to be the same in the BALB/c parent and dm2 mutant. Hybrid histocompatibility is a complex phenomenon but at this time we conclude that the H-2L locus is related to, if not identical to the Hh-1 gene but the H-2L locus is distinct from genes affecting the NK phenomenon.