S It remains unknown whether the normal adult liver contains bipotent stem/progenitor cells, and if it does, then what are the circumstances under which they proliferate. The aim of this study was to clarify whether the normal adult liver contains hepatic stem/progenitor cells, and if it does, will they be activated by extensive hepatectomy? Adult rat liver cells were isolated and cultured at a low-density, and the colony-forming assay was performed to evaluate the cell proliferative capacity. Immunocytochemistry and reverse transcription-polymerase chain reaction were used to investigate the multilineage differentiation capability. The rate of colony formation by cells from the normal liver and those from the regenerating liver after partial hepatectomy (PH) were compared to determine whether progenitor cell proliferation might be activated by PH. Only a few epithelial colonies (0.043+/-0.009% of nonparenchymal cells) continued to proliferate for more than 1 month. Reverse transcription-polymerase chain reaction and immnocytochemistry showed that these progenitor colonies expressed both hepatocyte and cholangiocyte markers. The proportion of progenitor cells that formed bipotential colonies did not differ significantly between the cells obtained from the normal and PH livers. Adult normal liver contains bipotent hepatic progenitor cells, but they are scarcely activated even after extensive hepatectomy.