Since trophic factors are increasingly recognized as playing a role in some decision-making steps during development, the influence of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) on the commitment of pluripotent neural crest cells was investigated by in vitro clonal analysis. BDNF caused an increase of up to 21-fold in the number of sensory neuron precursors per colony without a corresponding increase in the total number of cells. By contrast, BDNF treatment caused an equivalent decrease in the number of undifferentiated cells per colony. The data suggest that BDNF, but not NGF, directs pluripotent neural crest cells to differentiate along the primary sensory neuron lineage.