Dorsal root ganglia (DRG) midway through development require nerve growth factor (NGF) for survival and differentiation. These studies investigated when avian neural crest cells or DRG first exhibit high affinity NGF receptors in situ, and whether early embryonic cells expressing high affinity NGF receptors are responsive to NGF. Unfixed cryostat sections of quail embryos were exposed to varying concentrations of [125I]NGF to distinguish between high and low affinity binding. Radioautography revealed an absence of [125I]NGF binding on migrating neural crest cells in situ. Both high and low affinity NGF receptors were first detected in differentiating DRG at E3.5 (stage 23). The presence of high affinity receptors was additionally confirmed by identification of a high molecular weight complex on radioautographs of gels following cross-linking of [125I]NGF to dissociated DRG. The presence of high affinity NGF receptors in E3.5 DRG was unexpected since DRG have been reported to be unresponsive to NGF prior to the midpoint of development. Exposure of E3.5 DRG neuron-enriched cultures to exogenous NGF resulted in approximately 30% more neurons after 24 h in vitro. The effect of NGF was blocked by anti-NGF and was shown to be dose dependent. It remains to be determined whether the increase in cell number is due to a survival or mitogenic effect.