In peripheral nerves, ciliary neurotrophic factor (CNTF) is localized to a subset of Schwann cells and is decreased in synthesis during Wallerian degeneration. This pattern of expression is similar to that of myelin protein genes. In the present study, C57BL/Wld mice, which exhibit delayed Wallerian degeneration, were used to determine the role of axonal contact on the regulation of CNTF synthesis. Western blot analysis showed that CNTF immunoreactivity in Wld nerves remained almost normal even 10 days after ligation when it was almost undetectable in control mice. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis revealed that 4 days after ligation, concentrations of CNTF mRNA in Wld mice had decreased much less than in control mice, but that at 10 days CNTF mRNA concentrations in Wld and control mice were comparably low. These observations suggest that maintenance of axonal contact in the absence of axonal transport from the cell body delays the decrease of CNTF mRNA normally seen after injury. Also, during Wallerian degeneration in Wld mice, the decrease of CNTF protein is delayed for many days longer than the decrease in CNTF mRNA.