Ciliary neurotrophic factor (CNTF) promotes the survival of several populations of neurons, including sensory and motor neurons. Although CNTF is abundant in adult sciatic nerve, the mature protein lacks a signal sequence and is not secreted; therefore, it has been proposed to act as a lesion factor. The identification of a functional CNTF receptor revealed ligand-specific phosphorylation cascades and gene induction. However, it is not clear how these signal-transducing events are elicited in neuronal cell bodies that may be distant from the source of CNTF. We report here that CNTF can be retrogradely transported by adult sensory neurons. More importantly, sensory and motor neurons both show greatly increased transport of CNTF following peripheral nerve lesion. Axotomy-induced increases in retrograde transport of neurotrophic factors may be an important response of neuronal cell bodies during regeneration.