In vivo treatment of developing chick embryos with acidic and basic fibroblast growth factors (aFGF and bFGF) failed to affect the differentiation and survival of several populations of developing neurons in the CNS and PNS. All of the neuronal populations examined are known to undergo naturally occurring cell death, and they include spinal and cranial motoneurons, dorsal root ganglia, sympathetic ganglia, nodose ganglia, ciliary ganglia, and sympathetic preganglionic neurons in the PNS, as well as the accessory oculomotor nucleus, the isthmo-optic nucleus, and the brainstem auditory nuclei laminaris and magnocellularis in the CNS. Despite the lack of effect of bFGF on neuronal survival and differentiation, in vivo treatment increased the serum levels of bFGF and stimulated the proliferation of non-neuronal cells in the spinal cord. Therefore, although the administration of exogenous FGF to the developing chick embryo in vivo clearly has some biological activity in the CNS, it was nonetheless ineffective in promoting neuronal survival or differentiation. These data do not support the idea that FGF is a physiologically relevant neurotrophic agent in the developing avian nervous system.