The neoplastic transformation of bile duct changes induced by infections due to Clonorchis sinensis or Opisthorchis viverrini has been persistently debated because of the difficulty to establish the causative relation between those trematode infections and the development of primary carcinoma of the liver (PCAL) which has been found in Hong Kong, China, Korea and Thailand. The following observations, however, clearly support the hypothesis that clonorchiasis and opisthorchiasis are basic etiological factors of the pathogenesis of human cholangio-carcinoma (CC): C. sinensis and O. viverrini infections lead to quite similar tissue reactions in bile ducts, starting with desquamation of epithelial linings with subsequent development of adenomatous hyperplasia and periductal fibrosis besides inflammatory cellular exudation and goblet cell metaplasia in both man and experimental animals. The majority of PCAL are of the hepatocellular type but as to CC, the prevalence rate is much higher in those areas where C. sinensis and O. viverrini infections are endemic. Histologically, the neoplastic transformation from adenomatous hyperplasia in bile ducts to CC through dysplastic changes of lining cells or from cholangiofibrosis is clearly demonstrable. Furthermore, mucin-producing activity is also a frequent feature to reflect the neoplastic transformation of the metaplastic goblet cell change of the bile duct linings. Application of various carcinogens to liver fluke infected animals cause a higher incidence of CC than is the case in non-infected controls. These epidemiological and histopathologic characteristics seem to indicate that C. sinensis and O. viverrini are predisposing conditions for the pathogenesis of CC in Southeast and East Asian countries.