The morphological and phenotypic changes of sinusoidal endothelial cells in hepatocellular carcinoma were investigated along with the hemodynamic changes. Hepatocellular carcinomas, which were 10-20 mm in diameter, were obtained by liver aspiration biopsy. Twenty specimens of well differentiated and 20 specimens of moderately differentiated hepatocellular carcinoma were used. These were classified into two groups of hepatocellular carcinoma: with and without hypervascularity. Electron microscopy, immunohistochemistry using antibodies against factor VIII-related antigen, type IV collagen and laminin and lectin histochemistry using Ulex europaeus agglutinin I (UEA-I) were performed. Factor VIII-related antigen and UEA-1 binding sites were present in the sinusoidal endothelial cells in two groups. In hepatocellular carcinoma with hypervascularity, type IV collagen and laminin were present corresponding to basement membranes along the endothelial cells, which had few fenestrae. In another group, although type IV collagen was present along the endothelial cells that had a few fenestrae, laminin and basement membranes were rarely observed. These results suggest that the sinusoidal endothelial cells tend to show phenotypic changes in the early stage of hepatocarcinogenesis. As the arterial blood supply for hepatocellular carcinoma increases, the sinusoidal endothelial cells may form basement membranes and take on the morphological appearance of capillaries.