By using polymerase chain reaction-restriction length polymorphism and polymerase chain reaction-single-strand conformation polymorphism analysis, we screened 283 Japanese subjects [226 noninsulin-dependent diabetes mellitus (NIDDM), 12 impaired glucose tolerance, and 45 normal controls] for 2 amino acid polymorphisms, Ala513Pro and Gly972Arg, of the insulin receptor substrate-1. Only 8 NIDDM, 1 impaired glucose tolerance, and 1 normal subject were identified to be heterozygous for the Gly972Arg mutation, whereas no subject had an Ala513Pro polymorphism. The frequency of Gly972Arg was lower than recently reported in Danish and Finnish populations and was in good agreement with that previously reported in another Japanese cohort. Analysis of 1 pedigree of 1 NIDDM patient with a Gly972Arg showed no co-segregation between this polymorphism and the onset of NIDDM. Our results suggest that the Gly972Arg polymorphism does not play an important role in the pathogenesis of NIDDM in Japanese patients.