We have isolated mammalian neural crest cells using a monoclonal antibody to the low affinity NGF receptor, and established conditions for the serial propagation of these cells In clonal culture to assess their developmental potential. Thisanalysls indicates that, first, single mammalian neural crest cells are multlpotent, able to generate at least neurons and Schwann cells like their avlan counterparts. Second, multipotent neural crest cells generate multipotent progeny, indicating that they are capable of self-renewal and therefore are stem cells. Third, multlpotent neural crest cells also generate some clonal progeny that form only neurons orglia, suggesting the productlonof committed neuroblasts and glloblasts. Manipulation of the substrate alters the fate of the multlpotent cells. These findings have Implications for models of neural crest develop ment in vivo, and establish a system for studying the generation of cellular dlverslty by a multlpotent stem cell in vitro.