A systematic search for genetic linkage with maturity-onset diabetes of the young (MODY) as expressed in the R.-W. pedigree has been carried out. Evidence for linkage was found with restriction-fragment—length polymorphism loci that map to human chromosome 20. Two-point linkage analysis with CRI-L1214 (D20S16) and MODY gave a log of the odds (lod) score of 4.16 at Θ = 0.08. Multipoint linkage analysis with nine restriction-fragment–length polymorphism loci resulted in a lod score of 4.81 withthe MODY locus in an ∼20-cM region bounded by D20S16 and D20S14-D20S18. Examination of the pattern of MODY segregation suggests that additional factors, possibly geneticcould be involved in the age of onset of the disease.