A neoplastic human salivary intercalated duct cell clone was cultured in 5 microM 5-azacytidine for 5 days at 37 degrees C; then the cells were trypsinized and subcultured in growth medium without 5-azacytidine. Thereafter, subclones were cloned from the subculture. Of 12 subclones isolated, 7 clonal cell lines were established and characterized. The two subclones composed of cells which were spindle shaped or stellate exhibited phenotypes similar to those of myoepithelial cells such as microfibrils and myosin and formed a myoepithelioma upon transplantation of the cells into nude mice. The other five subclones were composed of polygonal cells with numerous secretory granules in their cytoplasm and containing amylase that seems to be specific to acinar cells; transplantation of these cells into nude mice resulted in production of acinic cell carcinoma. These findings indicate that a neoplastic human salivary intercalated duct cell is capable of at least bidirectional differentiation.