On Northern hybridization using the cDNA of type 2C protein phosphatase as a probe, substantial amount of the mRNA of type 2C protein phosphatase was detected in various organs of rats, suggesting that the type 2C protein phosphatase gene is a housekeeping gene. A relatively high level of the mRNA, however, was found in skeletal muscle compared with other organs. Similar results were obtained with the organs of mice. In addition, the mRNA level in C3H10T1/2 cells (embryonal mesenchymal cells of mice) was much lower than in mature skeletal muscle of mice. The mRNA level of type 2C protein phosphatase was enhanced in accordance with the differentiation of the C3H10T1/2 cells into myoblasts induced by the transfection of MyoD cDNA. These results suggest that type 2C protein phosphatase is related to the mechanism of differentiation of skeletal muscle cells.