Two cynomolgus monkeys were intravenously inoculated with a stool extract derived from Burmese patients who suffered from hepatitis E. The monkeys developed self-limiting acute hepatitis. Liver tissues were obtained sequentially by needle biopsy or at sacrifice. Histologically, the liver tissues exhibited necroinflammation which was characterized hy focal dropout of lymphocytes with accumulation of lymphocytes and macrophages. The severity of necroinflammation appeared to be parallel with elevation in serum aminotransferases. The lymphocytes in necroinflammation were positive for a cytotoxic/suppresser T (Leu-2a) immunophenotype. The hepatocytes surrounding focal necroses showed depletion of glycogen granules and decrease in glucose-6-phosphatase and succinic dehydrogenase activities. Ultrastructurally, damaged hepatocytes around the focal necroses revealed marked injurious change of the cytoplasmic organelles. Virus-like particles measuring approximately 27nm in diameter were observed in the hyaloplasm of damaged hepatocytes which frequently contacted with lymphocytes. These findings strongly suggested the immune-mediated hepatocytolysis in hepatitis E.