The localization of the cholestatic factor (CF) was immunocytochemically investigated in liver biopsy specimens obtained from patients with various liver diseases. CF was detected in seven of nine patients with drug-induced liver injury, three of four with acute viral hepatitis, three of five with alcoholic liver injury and in the two patients with autoimmune hepatitis. Fourteen of these 15 CF-positive patients had jaundice in their clinical courses. CF was stained diffusely in the cytoplasm of hepatocytes throughout the lobules in a granular pattern. Electron-microscopically, it was localized on the ribosomes and polysomes as well as on the filamentous structures around the bile canaliculi. However, CF was not detected in liver specimens from normal controls and patients with primary biliary cirrhosis and extrahepatic biliary obstruction. These findings suggest that CF plays an important role in intrahepatic cholestasis in various liver diseases.