ABSTRACT— Intrahepatic bile ducts were examined histologically and ultrastructurally in wedge-biopsied liver specimens from three patients with primary sclerosing cholangitis. Bile ducts with periductal concentric fibrosis, which is a characteristic finding in primary sclerosing cholangitis, revealed ultrastructurally finger-like projections or fine undulations of the basal free surfaces with markedly duplicated basal lamina. The lamina was collared by a layer of elongated fibroblasts and thickened bundles of collagen fibers outwards. These changes were consistently found in all sizes of ducts examined, and might be related to progressive periductal fibrosis. Serial section observations showed that some severely affected ducts actually disappeared when accompanying severe periductal fibrosis. It would therefore appear that progressive periductal fibrosis may interrupt fluid and nutrient exchange between the bile duct epithelia and peribiliary capillary plexus, followed by obliteration of the biliary lumina. Although the bile ducts showed segmentally periductal lymphocytic infiltration and, ultrastructurally, point contacts between infiltrating lymphocytes and biliary epithelial cells were observed occasionally, the exact role of infiltrating lymphocytes in the pathogenesis of primary sclerosing cholangitis remains unclear.