It is widely thought that mammalian Schwann cells do not express P-0, the major glycoprotein in peripheral myelin, unless they are induced to do so by axonal signals that can be mimicked by agents that trigger cAMP signaling pathways. In contrast, we find that cultured Schwann cells make large amounts of P-0 without the addition of any axonal-like signal, provided they have not been exposed to serum during the culture process. We also report that glial growth factor/neuregulin inhibits this constitutive P-0 expression. Myelin basic protein is regulated in a similar way. We suggest that expression of P-0 by Schwann cells before the onset of myelination may be prevented by inhibitory signals within the nerve, rather than by the absence of a positive signal from axons.