Leukemia inhibitory factor (LIF; also known as cholinergic differentiation factor) is a multifunctional cytokine that affects neurons, as well as many other cell types. To examine its neuronal functions in vivo, we have used LIF-deficient mice. In culture, LIF alters the transmitter phenotype of sympathetic neurons, inducing cholinergic function, reducing noradrenergic function, and altering neuropeptide expression. In vivo, a noradrenergic to cholinergic switch occurs in the developing sweat gland innervation, and changes in neuropeptide phenotype occur in axotomized adult ganglia. We find that the gland innervation of LIF-deficient mice is indistinguishable from normal. In contrast, neuropeptide induction in ganglia cultured as explants or axotomized in situ is significantly suppressed in LIF-deficient mice. Thus, LIF plays a role in transmitter changes induced by axotomy but not by developmental interactions with sweat glands.