Linkage analysis was performed on (C57BL/6J x TH)F1 x TH male backcross animals and (CAST/Ei x TH)F1 x TH male backcross animals to identify QTLs associated with diabetes-related phenotypes. The TH (TallyHo) strain is a mouse model for human non-insulin dependent diabetes mellitus (NIDDM). TH males develop hyperglycemia by 10-14 weeks of age whereas C57BL/6J and CAST/Ei males are normoglycemic. TH animals also exhibit increased body weight and fat pad weights compared to non-diabetic C57BL/6J and CAST/Eistrains. A locus associated with NIDDM, Tanidd1 (TallyHo associated NIDDM 1), mapped to mouse Chromosome 19 from 16 cM - 60 cM in both backcross sets (LOD = 3.1 at D19Mit103). Tanidd2 mapped to mouse Chromosome 13 from 5 cM - 70 cM in the C57BL6/J backcross (LOD = 4 at D13Mit148) and Tanidd3 mapped to mouse Chromosome 16 from 0 cM - 34 cM in the CAST/Ei backcross (LOD = 2.8 at D16Mit129). TH-derived alleles confer recessively inherited hyperglycemia at Tanidd1, Tanidd2, and Tanidd3. A QTL associated withbody weight, Tabw (TallyHo associated body weight), mapped to mouse Chromosome 7 from 0 cM - 44 cM (LOD = 3.9 at D7Mit231), and a QTL associated with fat pad weight, Tafat (TallyHo associated fat pad), mapped to mouse Chromosome 4 from 68 cM - 90 cM (LOD= 3.1 at D4Mit312). Animals homozygous for TH-derived alleles at Tafat exhibit lower fat pad weights than heterozygous animals, and animals homozygous for TH-derived alleles at Tabw exhibit lower body weights than heterozygous animals. The insulin gene, Ins1, maps near Tanidd1 and was considered as a candidate gene but sequence analysis failed to reveal differences between TH and C57BL/6J in the Ins1 promoter and coding regions.