Anterograde axonal transport of neurotrophins has been demonstrated recently, but to date such transport has only been shown for brain-derived neurotrophic factor and no other endogenous neurotrophin. Endogenous neurotrophin-3 (NT-3) protein is present in the ganglion cell layer of the chicken retina, as well as the superficial layers of the optic tectum. NT-3 immunolabel in these tectal layers is largely reduced or abolished after treatment of the eye with colchicine or monensin, demonstrating that endogenous NT-3 is transported to the optic tectum by retinal ganglion cells (RGCs). Reverse transcription-PCR analysis of RGCs purified to 100% shows that RGCs, but not tectal cells, express NT-3 mRNA. Blockade of the intercellular transfer of NT-3 within the retina does not reduce the anterograde transport of endogenous NT-3 to the tectum, indicating that a major fraction of the anterogradely transported NT-3 is produced by RGCs rather than taken up from other retinal cells. Immunolabel for the neurotrophin receptor p75, but not trkB or trkC, in the superficial tectum coincides with the NT-3 label. The p75 label in the neuropil of superficial tectal layers is largely reduced or eliminated by injection of monensin in the eye, indicating that p75 protein is exported along RGC axons to the retinotectal terminals and may act as a neurotrophin carrier. These results show that NT-3 is produced by RGCs and that some of this NT-3 is transported anterogradely along the axons to the superficial layers of the tectum, possibly to regulate the survival, synapse formation, or dendritic growth of tectal neurons.