The first neurons that differentiate in the embryonic foregut of mammals transiently express catecholamine biosynthetic enzymes and accumulate catecholamine. Since this transmitter is found predominantly in cells of the sympatho-adrenal (SA) lineage, it has been suggested that enteric and sympathetic neurons may derive from the same progenitor. Enteric neurons would then lose the catecholamine phenotype during further development, as the two lineages diverge. We have further investigated this possibility using the SA1 monoclonal antibody that binds selectively to SA progenitor cells in the embryonic rat. We find that SA1 binds to the tyrosine hydroxylase+, neurofilament+, and SCG10+ cells of the Embryonic Day 14.5 (E14.5) rat foregut. We also find that a marker for later neuronal differentiation in the SA lineage, B2, also appears in the myenteric plexus concomitant with the loss of SA1 staining. Thus, at least some enteric neuronal precursors may exhibit the SA1----B2 antigenic switch previously observed in developing sympathetic neurons at E14.5. SA1 staining in the foregut partially overlaps with staining for neuropeptide Y, vasoactive intestinal polypeptide, and serotonin. These results support the hypothesis that enteric and sympathetic neurons derive from a common progenitor and that as the markers for the SA lineage are down-regulated, the many types of enteric neurons begin to differentiate.