The proportion of subjects homozygous for DNA restriction fragments of a large size class (U alleles), in the polymorphic region flanking the 5' end of the insulin gene of chromosome 11, was higher in a group of non-insulin-dependent diabetic (NIDDM) patients than in normal controls. This finding confirms that the U allele is associated with at least one form of NIDDM. The U alleles were also found to be strongly associated with macroangiopathy in diabetic as well as in non-diabetic subjects. Thus, DNA sequences contained in the U alleles might be associated with the development of atherosclerosis in an as yet unknown way.