The genetics of hybrid susceptibility to parental myeloma transplants in histocompatible F1 hybrids was investigated. Various inbred mouse strains and their descendant congenic lines were crossed with BALB/C mice to produce appropriate F1 hybrids. Genetic inferences were drawn from the comparison of the frequencies of tumor graft takes among congenic combinations. Hybrids containing the C57BL/10 genetic background were less susceptible to myeloma transplants than were hybrids of other genotypes. Both H-2-associated and non-H-2-associated genetic factors played significant roles in determining host susceptibility to the transplants. The D end of the major histocompatibility complex did not play a predominant role in determining hybrid susceptibility in C57BL-derived F1 hybrids.