A total of 66 cases of well differentiated adenocarcinomas of the gallbladder comprising 12 mucosal carcinomas and 54 advanced carcinomas were examined histologically and immunohistochemically for metaplastic changes in the tumor tissue and non-neoplastic mucosa adjacent to the tumor tissue in order to elucidate the histogenesis of gallbladder carcinoma. Among the various kinds of metaplastic changes in the gallbladder mucosa, the occurrence of endocrine cells and lysozyme immunoreactivity were used as markers. The 66 cases of adenocarcinoma were divided into 12 cases showing no metaplastic changes (non-metaplastic type) and 54 cases containing at least one marker of metaplastic changes (metaplastic type). The frequency of metaplastic changes was compared between mucosal carcinoma and advanced carcinoma to determine whether these metaplastic changes could be a phenotypic expression of the original tissue from which the tumor was derived or a secondary phenomenon associated with the progression of the tumor. No difference could be observed between the two. Moreover, the carcinoma of the non-metaplastic type was often surrounded by an ordinary mucosa without metaplastic changes, whereas the carcinoma of the metaplastic type was frequently surrounded by a metaplastic mucosa. Some cases among the non-metaplastic type carcinomas showed a morphological transition between the ordinary mucosa and the carcinoma or contained the residue of ordinary type adenoma within the tumor. On the other hand, 5 cases of the metaplastic type carcinoma contained adenomatous residue of the metaplastic type. These results suggest that there might be two types of adenocarcinoma, one being derived from the ordinary epithelium of the gallbladder and the other from the metaplastic epithelium.