Nascent neural crest cells derived from explanted E12 embryonic rat caudal neural tubes were used as an assay system to investigate the effects of fibroblast growth factors on neural crest cell (NCC) survival, proliferation, migration, and differentiation. In vitro and in vivo all NCC express low affinity nerve growth factor receptors (p75-LNGFR), whereas a subpopulation of NCC expresses the carbohydrate epitope recognized by the monoclonal antibody HNK-1 (Bannerman and Pleasure, manuscript in preparation). Both acidic and basic fibroblast growth factor (FGF) promoted the survival of proportionally greater numbers of p75-LNGF+/HNK-1- than P75-LNGFR+/HNK-1+ NCC. An as yet uncharacterized factor present in neural tube-conditioned medium was also required for NCC survival. Mitosis was frequent in those NCC closest to the neural tube, less so as the cells migrated away. Neither basic nor acidic fibroblast growth factor (FGF) influenced rates of NCC mitosis in either of these locations, nor did these FGFs alter the rate at which nascent NCC migrated away from the neural tube. However, acidic and basic FGFs did delay the differentiation of neural crest derived neurons in the cultures. FGF is abundant in the embryonic rat neural crest outgrowth zone, and the present study strongly supports an essential role for FGF in early development of the mammalian neural crest.