Schwann cells produce myelin as an extension of their plasma membrane and ensheath nerve fibres in the peripheral nervous system (PNS). Several myelin proteins are common to both central nervous system (CNS) and PNS myelin but the major integral protein (Po) of PNS myelin is peculiar to this membrane (Greenfield et al . , 1973). Po comprises around 60% of the total protein of PNS myelin. SDS/polyacrylamide-gel analysis indicates an apparent M , of 28 00@30 000 and the protein is known to have a single N-linked oligosaccharide chain (Ishaque et al., 1980). Other post-translational modifications include acylation (Agrawal et al . , 1982). phosphorylation (Wiggins & Morell, 1980) and sulphation (Matthieu et al., 1975). The purpose of this work was to identify the subcellular site of synthesis of Po in Schwann cells and determine the mechanisms by which this protein is inserted into membranes before transport to the Schwann cell plasma membrane. mRNA isolated from sciatic nerves of 15-day-old rats was translated in a wheatgerm system and Po was immune precipitated and analysed on SDS-gels (Colman et ul., 1982). The primary translation product had a M , of 30700 compared with an M , of 28500 for the mature protein. This result indicated a cleavable signal sequence in the primary translation product of P,, mRNA. Removal of the single oligosaccharide from mature P,, with endoglycosidase F