The survival effects of brain-derived neurotrophic factor (BDNF) on the ganglion cells of the chick retina were studied in vitro at different embryonic ages. We found these effects to be strongly age-dependent: at E5, when the first ganglion cell axons have crossed the optic chiasm, but not yet reached the tectum, ganglion cells survived on a laminin substrate irrespective of the presence or absence of BDNF. At E6, when the axons of the first-generated ganglion cells reached the rostral pole of the tectum, the ganglion cells began to show a dependency on BDNF for survival, but the majority of them were alive after 2 days in vitro in the absence of BDNF. With increasing age, the BDNF dependency for survival increased, and at E11, the majority of the ganglion cells plated were dependent on BDNF for survival. It is at this age that the maximal number of axons can be found in vivo in the optic nerve, the subsequent elimination of ganglion cells and their axons resulting in the loss of hundreds of thousands of them over the next few days. Taken together, these data indicate that retinal ganglion cells depend on BDNF for survival only when their axons have reached their target in vivo. This situation is reminiscent of that described in the peripheral nervous system for the nerve growth factor responsiveness of mouse trigeminal sensory neurons during the period of innervation of their target.