The availability of cloned cDNA for the insulin receptor provides a means for evaluating the role of this gene in the high prevalence of NIDDM in American Blacks and Pima Indians. The frequencies of restriction fragment length polymorphisms (RFLPs) have been measured at this locus in a population of unrelated American Black lean and obese non-insulin dependent diabetics, further subdivided by age of diagnosis. The frequencies of these polymorphisms did not differ from those in a non-diabetic control population. This RFLP analysis was also used to evaluate DNA from 45 non-diabetic Pima Indians who were previously studied by the hyperinsulinemic euglycemic clamp technique. The frequencies of the polymorphic alleles did not differ between a group of low vs high glucose utilizers. A review of recently reported association studies in various racial groups, as well as linkage analysis studies in families, suggests the possibility that the insulin receptor locus may contribute in a minor way to diabetes susceptibility in some racial groups. This hypothesis needs further testing with molecular genetic methods.