Abstract: In the PNS, ciliary neurotrophic factor (CNTF) is found in significant amounts in the adult sciatic nerve, localized to myelin-related Schwann cells (SCs). Levels are undetectable in newborn but high in adult animals. After crush injury, CNTF production is reduced, recovering only as the nerve regenerates; if regeneration does not occur, CNTF levels remain low. We have examined the coupling of CNTF expression to myelination in vitro and in vivo to determine if axon-SC contact without myelination is sufficient to induce CNTF expression. Embryonic day 15 (E15) rat dorsal root ganglion (DRG) neuron and SCs were cocultured. CNTF was not detected in the DRGs either at E15 or after 2 days in vitro (div) by western blotting. However, after 10 div, CNTF could be identified and remained at constant levels up to 30 div. Depriving the cultures of ascorbic acid prevents myelination but not axon-SC contact. This did not affect CNTF protein production. Using reverse transcriptase-linked PCR (RT-PCR) techniques, no CNTF message was present in DRG from day 14 or 15 fetal rats; but by 6 days in culture, message was detected in both myelinating and nonmyelinating cultures. Isolated SC cultures, without axonal contact, failed to express CNTF protein; however, mRNA was detected by RT-PCR. Embryonic SC can be induced to synthesize CNTF in culture by axonal contact. Active myelination is not required.