Sympathetic neurons differentiate from a developmentally restricted progenitor cell in the neural crest-derived sympathoadrenal lineage. We have isolated these progenitors by fluorescence-activated cell sorting and immortalized them using a v-myc-containing retrovirus. The complement of antigenic markers expressed by these lines suggests that they have retained many of the properties of their normal counterparts. These lines initiate neuronal differentiation in response to basic FGF, but not to NGF, and do not contain NGF receptor mRNA. In NGF plus FGF, however, a small percentage of the cells differentiate to NGF-dependent postmitotic neurons. Furthermore, an induction of NGF receptor mRNA can be observed in response to FGF. Thus, the development of sympathetic neurons may involve a relay, in which FGF both initiates differentiation and induces the NGF receptor, which in turn controls further maturation and survival.