Susceptibility genes for thyrotropin receptor (TSHR) antibodies and hyperthyroidism can be probed in recombinant inbred (RI) mice immunized with adenovirus expressing the TSHR A-subunit. The RI set of CXB strains, derived from susceptible BALB/c- and resistant B6- mice, were studied previously. High-resolution genetic maps are also available for RI BXH strains, derived from B6 and C3H/He parents. We found that C3H/He mice develop TSHR antibodies and some animals become hyperthyroid following A-subunit immunization. In contrast, the responses of the F1 progeny of C3H/He x B6 mice, as well as most BXH RI strains, are dominated by the B6 resistance to hyperthyroidism. As in the CXB set, linkage analysis of BXH strains implicates different chromosomes or loci in the susceptibility to induced TSHR antibodies versus hyperthyroidism. Importantly, BXH and CXB mice share genetic loci controlling the generation of TSHR antibodies (Chr 17, MHC region, and Chr X) and development of hyperthyroidism (Chr 1 and 3). Moreover, some chromosomal linkages are unique to either BXH or CXB strains. An interesting candidate gene linked to thyroid stimulating antibody generation in BXH mice is the immunoglobulin heavy chain locus, suggesting a role for particular germline region genes as precursors for these antibodies. In conclusion, our findings reinforce the importance of MHC region genes in controlling the generation of TSHR antibodies measured by TSH binding inhibition. Moreover, these data emphasize the value of recombinant inbred strains to dissect the genetic basis for induced TSHR antibodies versus the their effects on thyroid function in Graves' disease.