BACKGROUND/AIMS: Cholesterol gallstones which are the most common gallbladder stone found in Western countries are recently increasing in Orient including Korea. The formation of cholesterol stone is frequently associated with changes in cholesterol and bile acid metabolism. Apolipoprotein (apo) E is a genetically polymorphic protein influencing lipoprotein metabolism. The aim of this study was to evaluate whether apo E polymorphism is related to the development of gallstone or bil duct stone. METHODS: Apo E phenotype was determined in 132 patients with biliary stone (95 gallstones, 37 bile duct stones) and 49 controls without stone. We determined apo E phenotype by polymerase chain reaction and line probe assay with reverse hybridization principle using allele-speci fic oligonucleotide probe. RESULTS: The E4/3 phenotype (21.0%) and 4 allelic frequency (0.15) were significantly higher in patients with gallbladder stones than in patients with bile duct stones and controls (p<0.05). The differences in apo E phenotype and 4 allelic frequency between the patients with bile duct stones and controls were not significant. Low-density lipoprotein (LDL) cholestero level of E4/3 phenotype was significantly higher than that of other phenotypes (p<0.05). CONCLUSIONS: The apo E4 isoform of apo E may be associated with the development of gallstones.