PURPOSE: Although many strides have been made in the radiological and laboratory diagnosis, the liver biopsy is still considered an important tool for the diagnosis of liver disease. We report our experience that histologic investigation of the liver was essential searching for the etiologic diagnosis in eight children with fever of unknowm origin and hepatosplenomegaly, who's diagnosis were not documented by other diagnostic studies. METHODS: Histologic investigation of the liver including Percutanous liver biopsy, open surgical biopsy, necropsy or autopsy was taken at Seoul national university of children's hospital between 1985 and 1995 in twelve children with fever of unknown origin and hepatosplenomegaly. We performed light and electron microscopic examination, culture and PCR of the tissue obtained by liver biopsy. RESULTS: 1) The etiologic diagnoses were possible by histologic investigation of the liver in 9 of 12 Cases; Nine cases were congenital tuberculosis, cryptococcosis, hepatic capillariasis, candidiasis, amoebiasis, neonatal herpes hepatitis, Escherichia. coli abscess and two cases of cytomegalovirus hepatitis. Three cases in which organisms could not be found in tissue obtained from biopsy were suspected clinically as liver abscess and parasite infestation. 2) Three cases were males and 6 were females, ranging in age from 1 days to 6 years; mean age 23.6 months. 3) Clinical manifestations were fever of unknown origin(9 Cases), hepatomegaly(9 Cases), splenomegaly(5 Cases), skin lesions(2 Cases) and jaundice(3 Cases). 4) Laboratory findings were increased AST/ALT(7 Cases), hyperbilirubinemia(3 Cases), leukocytosis(5 Cases), eosinophilia(2 Cases), increased CRP(9 Cases) and increased ESR(5 Cases). 5) In four children, there were underlying diseases which were acute lymphoblastic leukemia, acute myeloid leukemia and two cases of prematures. CONCLUSIONS: In children with fever of unknown origin and hepatosplenomegaly, we recommend liver biopsy for early diagnosis and apropriate management.