We recently proposed that ciliary neurotrophic factor (CNTF) shares two receptor components with a generally acting cytokine, leukemia inhibitory factor (LIF), but that CNTF also requires a third receptor component (CNTFRalpha) that is mostly restricted to the nervous system in its expression. Here we demonstrate that a transfected CNTFRalpha gene is sufficient to confer CNTF responsiveness upon hemopoietic cells normally responsive only to LIF, providing evidence that CNTFRalpha is a required receptor component that uniquely characterizes CNTF-responding cells. Consistent with this notion, CNTFRalpha expression could be localized to neurons within all known peripheral targets of CNTF. CNTFRalpha was also widely expressed within neurons of the CNS, suggesting that CNTF has broader CNS actions than previously appreciated. However, in vivo localization of CNTFRalpha, as well as of CNTF itself, is consistent with a particularly important role for CNTF in motor function as well as during neuropoiesis.