Glucagon-like peptide-1 (GLP-1) stimulate glucose dependent insulin secretion from beta-cells. Human cDNA and the gene of the receptor for the GLP-1 was isolated. Two polymorphic simple tandem repeats were found in the gene. Using these markers, role of GLP-1 receptor mutations in the pathogenesis of NIDDM was studied. No association was found between the marker alleles and NIDDM in African American or in Japanese. Linkage was rejected between the GLP-1 receptor gene and NIDDM in Caucasian late-onset NIDDM families and in French MODY families. Mutations in the GLP-1 receptor gene do not appear to be major genetic determinants of NIDDM. Further studies are required to exclude the minor role of the gene in a fraction of NIDDM patients.