Experiments were done to study the fate of transient catecholaminergic (TC) cells that develop in the rodent gut during ontogeny. When they are first detected, at Day E11 in rats, TC cells are distributed along the vagal pathway, in advance of the descending fibers of the vagus nerves, and in the foregut. The early TC cells coexpress the immunoreactivities of several neural markers, including 150-kDa neurofilament protein, peripherin, microtubule associated protein (MAP) 5, and growth-associated protein (GAP)-43, with those of the catecholamine biosynthetic enzymes tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH). All cells in the fetal rat bowel at Day E11 that express neural markers also express TH immunoreactivity. The primitive TC cells also express the immunoreactivities of neural cell adhesion molecule (N-CAM), neuropeptide Y (NPY), and nerve growth factor (NGF) receptor (and NGF receptor mRNA). By Day E12 TC cells are found along the vagal pathway and throughout the entire preumbilical bowel. At this age TC cells acquire additional characteristics, including MAP 2 and synaptophysin immunoreactivities and acetylcholinesterase activity, which indicate that they continue to mature as neurons. In addition, TC cells of the rat are immunostained at Day E12 by the NC-1 monoclonal antibody, which in rats labels multiple cell types including migrating cells of neural crest origin. Despite their neural properties, at least some TC cells divide and therefore are neural precursors and not terminally differentiated neurons. At Day E10 TH mRNA-containing cells were not detected by in situ hybridization; however, by Day E11 TH mRNA was detected in sympathetic ganglia and in scattered cells in the mesenchyme of the foregut and vagal pathway. At this age, the number of enteric and vagal cells containing TH mRNA is about 30% less than the number of cells containing TH immunoreactivity in adjacent sections. The ratio of TH mRNA-containing cells to TH-immunoreactive vagal and enteric cells is even less at Day E12, especially in more caudal regions of the preumbilical bowel. A similar decline in the ratio of TH mRNA-containing to TH-immunoreactive cells was not observed in sympathetic ganglia. After Day E12 TH mRNA cannot be detected in enteric or vagal cells by in situ hybridization; nevertheless, TH immunoreactivity continues to be present through Day E14. DBH, NPY, and NGF receptor immunoreactivities are expressed by TH-immunoreactive transitional cells in the fetal rat gut after TH mRNA is no longer detectable.(ABSTRACT TRUNCATED AT 400 WORDS)