Using an electron-microscopic, enzyme-labeled antibody method and cytochemical method in addition to conventional electron microscopy, we investigated the mechanism by which serum amyloid A protein (SAA) and amyloid fibrils were formed in the liver of mice with experimental amyloidosis. After induction, SAA was found initially on the rough endoplasmic reticulum of hepatocytes followed sequentially by the Golgi apparatus and secretory granules of hepatocytes. Shortly afterwards, SAA was observed in Disse's spaces, hepatic sinusoids and Kupffer cells. Amyloid fibrils appeared to accumulate predominantly extracellularly in the cytoplasmic invaginations of Kupffer cells or hepatocytes. However, they seemed to be partially formed by lysosomal enzymes in the cytoplasm of Kupffer cells.