Translocation of mRNAs has emerged as an important form of protein targeting. In oligodendrocytes, the myelin-forming cells of the central nervous system, myelin basic protein (MBP) mRNAs are transported into cell processes and the cytoplasmic channels that infiltrate the myelin sheath. This mRNA movement is important for myelination and occurs in purified oligodendrocytes in vitro, but not in oligodendrocytes grown on bed layers of astrocytes. We have shown previously that this astrocytic inhibition depends on cell-cell contact and is partially relieved in primary cultures that contain some neurons in addition to oligodendrocytes and astrocytes. We report here that soluble factors, secreted by neurons, are responsible for relieving the astrocytic inhibition of MBP mRNA translocation. Of several growth factors tested, only platelet-derived growth factor (PDGF) was effective in alleviating the astrocytic inhibition. Double immunofluorescence analysis demonstrated the presence of PDGF alpha-receptors in oligodendrocytes. PDGF appears to mediate its effect via its alpha-receptors and receptor tyrosine kinases. This interaction among the three neural cell types may play an important role in regulating remyelination after injury.