Ciliary neurotrophic factor (CNTF) is a 22-kDa protein predicted to share with leukemia inhibitory factor (LIF) and interleukin-6 a common amphipathic helical domain. Consistent with this prediction, the CNTF receptor complex is composed of the CNTF alpha receptor, the LIF beta receptor and gp130 a signalling molecule for LIF and interleukin-6. The major sources of synthesis of CNTF are Schwann cells and astrocytes, but it remains unclear how much CNTF is released from these glial cells and by what mechanism. In vitro, CNTF supports the survival of all classes of peripheral nervous system neurons plus many CNS neurons, induces neurite outgrowth, promotes a cholinergic phenotype in sympathetic neurons and arrests division of neuronal precursor cells. Several cell lines also respond to CNTF. In vivo, CNTF rescues several types of neurons from axotomy-induced death. The functions of CNTF in the development and maintenance of the nervous system remain enigmatic.