Ciliary neurotrophic factor (CNTF) has a variety of effects on different neuronal populations in vitro, but little has been reported concerning its effects in vivo. This study examined the effects of CNTF administration on peripheral nerves both in young growing rats and in more mature animals. In both young and fully grown rats, CNTF stimulated levels of substance P and calcitonin gene related peptide in sensory spinal ganglia. In immature rats, CNTF increased compound nerve conduction velocity and motor nerve conduction velocity. By contrast, electrophysiological measurements were not affected in fully grown animals. There was a biphasic dose response to CNTF for the electrophysiologic changes with larger changes noted at a dose of 0.1 micrograms/g body weight than at a dose of 0.25 micrograms/g. There were no behavioral changes noted at either dose of the factor. These observations indicate that CNTF administration in vivo can influence neural physiology, and suggest that the factor may be useful for the treatment of disorders involving either sensory or motor peripheral nerves.