Explant and dissociated neuron-enriched cultures of nodose ganglia (inferior or distal sensory ganglion of the X th cranial nerve) were established from chick embryos taken between embryonic Day 4 (E4) and Day 16 (E16). The response of each type of culture to nerve growth factor (NGF) was examined over this developmental range. At the earliest ages taken (E4–E6), NGF elicited modest neurite outgrowth from ganglion explants cultured in collagen gel for 24 hr, although the effect of NGF on ganglia taken from E4 chicks was only marginally greater than spontaneous neurite extension from control ganglia of the same developmental age. The response of nodose explants to NGF was maximal at E6–E7, but declined to a negligible level in ganglia taken from E9–E10 or older chick embryos. In dissociated neuron-enriched cultures, nodose ganglion neurons were unresponsive to NGF throughout the entire developmental age range between E5 and E12. In contrast to the lack of effect of NGF, up to 50% of nodose ganglion neurons survived and produced extensive neurites in dissociated cultures, on either collagen- or polylysine-coated substrates, in the presence of extracts of late embryonic or early posthatched chick liver (E18–P7). Antiserum to mouse NGF did not block the neurotrophic activity of chick (or rat or bovine) liver extracts. Whether cultured with chick liver extract alone or with chick liver extract plus NGF, nodose ganglion neurons taken from E6–E12 chick embryos and maintained in culture for 2 days were devoid of NGF receptors, as assessed by autoradiography of cultures incubated with 125I-NGF. Under similar conditions 70–95% of spinal sensory neurons (dorsal root ganglion—DRG) were heavily labeled. In contrast to the lack of NGF receptors on placode-derived neurons, the satellite cells of the early (E5–E8) nodose ganglion, which are neural-crest derived, were found to possess NGF receptors. We conclude from this study that sensory neurons, such as those of the nodose ganglion, derived from neurogenic placodes have neurotrophic growth factor requirements which are distinct from those of neural-crest derived sensory neurons. We propose that the modest fiber outgrowth that NGF elicits from explants of nodose ganglia taken from E4–E8 chick embryos is not a response of placodal neurons but is indicative of the derepression and expression in vitro of neuronal potentialities contained within the neural-crest derived cells that normally give rise only to the satellite cells of the nodose and other cranial sensory ganglia.