DEVELOPMENT and maintenance of the mammalian nervous system is dependent upon neurotrophic cytokines. One class of neurotrophic factor acts through receptor complexes involving the low-affinity leukaemia inhibitory factor receptor subunit (LIF-R)(1-3). Members of this family of cytokines, such as ciliary neurotrophic factor (CNTF) and leukaemia inhibitory factor (LIF), have profound effects on the survival and maintenance of motor neurons(4-10). Recently it was reported that mice lacking LIF-R die shortly after birth(11) unlike mice lacking CNTF or LIF which are viable. Here we describe histopathological analyses of lifr mutants that reveal a loss >35% of facial motor neurons, 40% of spinal motor neurons and 50% of neurons in the nucleus ambiguus. These findings point to the existence of a ligand for LIF-R that is required for the normal development of motor neurons in both brainstem nuclei and spinal cord.