Immunocytochemical localization of the protein product of the proto-oncogene c-fos allows anatomical identification of physiologically activated neurons. The present study examined the subnuclear distribution of cFos protein in the rat caudal medulla following peripheral administration of cholecystokinin octapeptide, which reduces feeding and gastric motility by a vagally mediated mechanism. To begin phenotypic characterization of neurons activated to express cFos following cholecystokinin treatment, double-labeling techniques were used to identify vagal motor neurons and neurons immunoreactive for tyrosine hydroxylase, neuropeptide Y, and neurotensin. Activated cells were most prevalent in the subnucleus medialis of the nucleus of the solitary tract, less prevalent in the subnucleus commissuralis, and virtually absent in the subnuclei centralis and gelatinosus. Many activated cells occupied the caudal area postrema; some of these were catecholaminergic. In contrast, activated cells were sparse within the medial rostral area postrema. Other activated cells occupied the dorso- and ventrolateral medulla and the midline raphe nuclei. Retrograde labeling of vagal motor neurons confirmed that very few were activated. Those that were activated occupied the caudal dorsal motor nucleus. In the dorsomedial medulla, 51% of catecholaminergic neurons and 39% of neurons positive for neuropeptide Y were activated, but no neurotensin-positive neurons were activated. In the ventrolateral medulla, 25% of catecholaminergic neurons and 27% of neuropeptide Y-positive neurons were activated. By characterizing the subnuclear distribution and chemical phenotypes of neurons activated by exogenous cholecystokinin, these data contribute to elucidation of the neural circuits mediating the behavioral, physiological, and neuroendocrine effects produced by this peptide.