Objectives: Hereditary unconjugated hyperbilirubinemias including Crigler-Najjar syndrome type Ⅰ, type Ⅱ and Gilbert syndrome are caused by mutations of the bilirubin UDP-glucuronosyltransferase gene UGT1A 1.In infantile period, the mutations of UGT1 A 1 also induce prolonged unconjugated hyperbilirubinemia in assicociate with breast milk ingestion (breast milk jaundice).Genetic analysis of UGT1A1 is helpful for diagnosis of those hyperbilirubinemia.However, some difficulty for differential diagnosis of the syndromes remains.We analyzed genotypes of 161 Japanese patients and consider whether genotype provides a suitable criterion for differential diagnosis of the syndromes.Patients and methods: Japanese patients (96 males and 65 females) with unconjugated hyperbilirubinemia were analyzed.Their serum bilirubin concentrations varied from 1.2 to 19.4 mg/dl (2 1 to 331 μM).Gene analysis of UGT1A 1 was performed with PCR-amplified direct sequencing.Association between serum bilirubin concentrations and genotypes were analyzed.Results: Most patients (117/161) had more than 3 mutations.The major mutation in Crigler-Najjar syndrome type Ⅱ (8/16), based on serum bilirubin concentration, was homozygous G71R + Y486D.Three prevalent genotypes of Gilbert syndrome were homozygous T-3279G-+A(TA)7TAA, compound heterozygous T-3279G+A(TA)7TAA/G71 R, and homozygous G71R.The serum bilirubin concentrations of 12.4% of patients was distributed above the concentration range for Gilbert syndrome but below that for Crigler-Najjar syndrome type Ⅱ [from 4.1 to 5.9 mg/dl (70 μM to 101 μM)].Except for homozygous G71R+Y486D, differences in serum bilirubin concentrations between the genotypes were not significant.Conclusion: Most patients had more than 3 mutations, and genetic trait of the hyperbilirubinemias was principally autosomal recessive.The serum bilirubin concentration varied continuously from Gilbert to CriglerNajjar syndrome type Ⅱ depending on genotype.This study indicates that the border between Crigler-Najjar syndrome type Ⅱ and Gilbert syndorme is not clear.