Iddm4 is a dominant non-major histocompatibility complex (MHC) determinant of diabetes susceptibility in BBDR rats treated with poly I:C, plus depletion of regulatory T cells. In congenic MHC-identical normalWFrats, Iddm4d sensitively and specifically predicts induced diabetes. We report a new diabetes-susceptible subcongenic line that carries Iddm4 in a <2.6 megabase interval. Candidate genes include the T cell receptor β chain variable (TCRVβ) family. We found that TCRVβ4 in WF rats contains a stop codon, whereas 5/5 diabetes-susceptible rat strains express TCRVβ4. We conclude that Iddm4-mediated diabetes resistance in rats may be due to a recessive protective mutation in TCRVβ4.