Sinusoidal inclusion-containing endothelial cells in the liver were investigated with particular interest in their capacity of metabolizing immunoglobulin. Formalin-fixed deparaffinized liver specimens were used for immunohistochemistry, and pronase digestion was proved to be effective for antigen retrieval of immunoglobulin. The inclusions in sinusoidal endothelial cells were strongly immunostained with anti-immunoglobulin (Ig)G, IgA, and IgM antibodies in predigested sections. The complements were not identified immunohistochemically in the inclusions even after pronase treatment. Two women with autoimmune liver disease, who initially represented high levels of serum γ globulin and abundant inclusion-containing endothelial cells, were studied. The subsequent biopsy after effective corticosteroid therapy demonstrated significant histological improvement as well as the disappearance of inclusion-containing endothelial cells (ICECs). During and after treatment, their serum γ globulin levels were drastically reduced. In conclusion, the hepatic sinusoidal endothelial cells can take up serum immunoglobulin, probably through a receptor-mediated pathway, and its excessive storage results in the formation of cytoplasmic inclusions that are easily recognized by a light microscope. The stored immunoglobulin may be degraded in the cytoplasm, and the inclusions would disappear in association with the reduction of sinusoidal γ globulin content. In other words, the intralobular density of inclusion-containing endothelial cells is a morphological predictor for the serum γ globulin level. (Hepatology 1995; 22:1456–1461).