The Ca(2+)- and Zn(2+)-binding S-100 proteins (S100) are predominantly localized in astrocytes of adult mammalian brain. In addition, light and electron microscopic immunocytochemistry revealed S100 in a small subpopulation of oligodendrocytes. By nuclear morphology and abundance of rough ER and Golgi fields, these cells resembled actively myelinating oligodendrocytes. S100 immunoreactivity was also found in paranodal loops and outer mesaxons of isolated of myelin sheaths. Data suggests that oligodendroglial content of S100 relates to cell turnover and/or myelin repair in the adult rat brain, and that S100 is present during myelin compaction.