Development of diabetes in NOD mice is polygenic and dependent on both major histocompatibility complex (MHC)-linked and non-MHC-linked insulin-dependent diabetes (Idd) genes. In (F1 x NOD) backcross analyses using the B10.H-2g7 or B6.PL-Thy1a strains as the outcross partner, we previously identified several non-MHC Idd loci, including two located on chromosome 3 (Idd3 and Idd10). In the current study, we report that protection from diabetes is observed in NOD congenic strains having B6.PL-Thy1a- or B10-derived alleles at Idd3 or Idd10. It is important to note that only partial protection is provided by two doses of the resistance allele at either Idd3 or Idd10. However, nearly complete protection from diabetes is achieved when resistance alleles are expressed at both loci. Development of these congenic strains has allowed Idd3 to be localized between Glut2 and D3Mit6, close to the Il2 locus.