Contrary to widely held beliefs, the gene encoding proteolipid protein (PLP), the major structural protein of central nervous system myelin, is expressed in Schwann cells and their tumors. Proteolipid mRNA was identified in human acoustic neuromas and in rat and rabbit sciatic nerves using a human PLP cDNA as a probe. Proteolipid protein itself was shown to be present in human and rat sciatic nerve Schwann cells by immunofluorescence microscopy and by Western blot analysis using antisera raised to a synthetic PLP polypeptide. Although easily detected in the Schwann cell body, PLP was not detected in the peripheral myelin itself, suggesting that the PLP is preferentially excluded from this portion of the Schwann cell membrane.