DNA variation related to the insulin receptor gene was studied with the restriction endonucleases Sst 1 and Bgl II. These identified 4 alleles, termed S1 (5.3 kilobases), S2 (5.8 kilobases), B1 (23.4 kilobases) and B2 (20.0 kilobases). Random association between these two insulin receptor polymorphisms was found in all of the study groups. The frequencies of genotypes possessing the S2 allele in Caucasian controls (n = 54), race matched non-insulin dependent diabetics (n = 56) and insulin dependent diabetics (n = 34) were 0.06, 0.18 and 0.04 respectively (p less than 0.01 for NIDDM versus IDDM or controls by chi-squared test). There were no significant differences in frequencies of genotypes with the B1 or B2 alleles amongst these three groups. The S2 allele or adjacent loci may provide a useful genetic marker for NIDDM.