Ciliary neurotrophic factor (CNTF) was first identified as a trophic activity that was able to support the survival of chick ciliary ganglion (CG) neurons in vitro. CNTF from rabbit and rat were subsequently purified from sciatic nerve and their cDNA sequences cloned. Another trophic molecule for CG neurons was identified as a growth promoting activity (GPA). GPA was purified from chicken sciatic nerve and cloned from embryonic chicken eye. The rat and rabbit CNTFs have a considerable amount of structural homology and are not secreted in significant quantities, whereas GPA is less similar in that it is only 49% homologous with rabbit and rat CNTF and is secreted by cells. This review discusses other similarities and differences in biological activities, molecular structure, receptor signaling and cellular distribution between CNTF and GPA and suggests that these molecules may have different functions in rodents and birds.