It has been suggested that many, if not all crest-derived neurons develop from a limited subpopulation of neurogenic precursors. To develop cell-type specific markers that identify these precursors directly we have used differential screening of crest-derived cell populations known to have, or not to have, neurogenic ability. We have determined that the neuron-specific human auto-antibodies designated Anti-Hu bind to cytoplasmic and nuclear determinants not only in mature avian neurons and neuroendocrine cells but also in subpopulations of morphologically non-neuronal avian crest-derived cells. Significantly, these Anti-Hu+ non-neuronal crest-derived cells are present only in populations that have neurogenic ability and are absent from populations that lack neurogenic ability. Moreover, following additional development in vivo or in vitro, Anti-Hu+ non-neuronal crest-derived cells appear to express other neuronal traits. These results suggest that Anti-Hu-immunoreactivity is an early indicator of neurogenesis among crest-derived cells, and that Anti-Hu+ non-neuronal cells are either neurogenic precursors or immature neurons. Similarly, using the same differential screening paradigm, we have identified two monoclonal antibodies, designated 12E10 and 17F5, which also label both neurons and some apparently nonneuronal cells in neurogenic populations of neural crest cells. Anti-Hu-IR appears to precede expression of either of these two markers.