Heterozygous mutations in the genes encoding transcription factors (HNF-1alpha, HNF-1beta and HNF-4alpha) in the hepatocyte nuclear factor (HNF) network are associated with maturity-onset diabetes of the young (MODY). We screened HNF-6 gene for mutations in 34 Japanese subjects with MODY/early-onset diabetes mellitus and 56 subjects with late-onset diabetes mellitus. One single nucleotide polymorphism (SNP) at codon 287 (GGG to GGT) was found in the gene and the frequency was similar among MODY/early-onset diabetes, late-onset diabetes and control subjects. Genetic variations in the HNF-6 gene are not likely to contribute to the susceptibility to diabetes mellitus in Japanese.