No proteases have been identified to be oligodendrocyte-specific though there are phenomena in which proteases may be committed. We have cloned a cDNA for mouse homologue of protease M/neurosin, serine protease, and localized its mRNA in the mouse brain. The cDNA and the deduced amino acid sequences were 66% identical to those of human protease M/neurosin. In situ hybridization histochemistry revealed that the mRNA was localized in the mature oligodendrocytes which expressed proteolipid protein mRNA. Developmentally, protease M/neurosin mRNA was expressed by oligodendrocytes 2 to 7 days after the maturation. Thus, protease M/neurosin may be important to the processes occurring after the maturation of oligodendrocytes such as myelination or turnover of the proteins in the myelin.