The projections of the nucleus of the solitary tract (NST) were studied by autoradiographic anterograde fiber-tracing and horseradish peroxidase (HRP) retrograde cell-labeling. Tritiated proline and leucine were deposited in electrophysiologically identified regions of NST. Injections of NST at levels caudal to where the vagus enters the nucleus, from which responses were evoked by stimulation of cranial nerves IX and X, revealed topographically organized bilateral projections to, most prominently, the ventrolateral medullary reticular formation which contains neurons of the ambiguus complex, and to the lateral and medial parabrachial nuclei, including a small portion of the medially adjacent central gray substance. Labeled fibers in the ventrolateral reticular formation were present from the nucleus retroambigualis rostralward to the retrofacial nucleus, with the densest concentration located over the nucleus ambiguus proper. The parabrachial projection was confirmed using HRP and shown to originate from cells in the medial subdivision of NST. Due to the problem of fibers en passant, it was not possible to interpret conclusively the cell-labeling seen around the solitary tract after HRP injections made in the region of the nucleus ambiguus. Labeled fibers were also traced from caudal NST to the dorsal motor nucleus of the vagus, but their origin could not be determined with certainty. Other labeled axons, traced to circumscribed parts of the inferior olivary complex and via the contralateral medial lemniscus to VPL of the thalamus, were shown in HRP experiments to originate from the dorsal column nuclei rather than NST. No labeled fibers were traced into the spinal cord, nor were any cells labeled in NST after large HRP deposits in upper cervical segments. Isotope deposits at levels of NST rostral to the entrance of the vagus, from which responses were evoked by rapid stimulation of the tongue, revealed an ipsilateral projection which ascends as a component of the central tegmental tract to the parvicellular part of the ventral posteromedial thalamic nucleus (VPMpc). After small HRP deposits in VPMpc, labeled cells in NST were restricted to the rostral part of the lateral subdivision. No labeled axons were traced from rostral NST to the ambiguus complex or parabrachial area. Injections of 3H-amino acids at intermediate levels of NST resulted in fiber-labeling in VPMpc, the parabrachial area, and the ambiguus complex.