Neural crest cells migrate extensively and give rise to diverse cell types, including cells of the sensory and autonomic nervous systems. A major unanswered question concerning the neural crest is when and how the neural crest cells become determined to adopt a particular fate. We have explored the developmental potential of trunk neural crest cells in avian embryos by microinjecting a vital dye, lysinated rhodamine dextran (LRD), into individual cells within the dorsal neural tube. We find that premigratory and emigrating neural crest cells give rise to descendants with distinct phenotypes in multiple neural crest derivatives. These results are consistent with the idea that neural crest cells are multipotent prior to their emigration from the neural tube and become restricted in phenotype after emigration from the neural tube either during their migration or at their sites of localization. To determine whether neural crest cells become restricted during their migration, we have microinjected individual trunk neural crest cells with dye shortly after they leave the neural tube or as they migrate through the somite. We find that a majority of the clones derived from migrating neural crest cells appear to be multipotent; individual migrating neural crest cells gave rise to both sensory and sympathetic neurons, as well as cells with the morphological characteristics of Schwann cells, and other nonneuronal cells. Even those clones contributing to only one neural crest derivative often contained both neurofilament-positive and neurofilament-negative cells. These data demonstrate that migrating trunk neural crest cells, like their premigratory progenitors, can be multipotent. They give rise to cells in multiple neural crest derivatives and contribute to both neuronal and non-neuronal elements within a given derivative. Thus, restriction of neural crest cell fate must occur relatively late in migration or at the final destinations.