Background: The caudal ventrolateral medulla (CVLM), an area having cardiovascular and respiratory functions, contains neurons that project to the thoracic spinal cord. It has been presumed, although never demonstrated, that the CVLM thoracic projections terminate on intercostal and sympathetic motor neurons. Using a combination of tracers, the purpose of the present study was to describe a route through which the CVLM may directly influence sympathetic and intercostal motor neurons. Methods: To label the medullospinal projections orthogradely, either biotinylated dextran amine or lectin conjugated horseradish peroxidase was injected into the CVLM. To label the intercostal and sympathetic motor neurons retrogradely, cholera toxin subunit B-horseradish peroxi-dase was injected into the intercostal muscles and superior cervical ganglion. Subsequently, projections from the CVLM were observed to terminate on, or in close proximity to, sympathetic and intercostal motor neurons. Results: Projections to sympathetic neurons were largely ipsilateral, whereas projections to intercostal neurons were primarily contralateral. In retrograde labeling experiments, it was observed that many of the CVLM-thoracic projections originated from the nucleus retroambiguus. Conclusions: The finding that the CVLM projects to sympathetic and intercostal motor neurons supports its role in cardiovascular and respiratory functions. The authors suggest that CVLM influences upon sympathetic motor neurons may be inhibitory. Anat. Rec. 250:95-102, 1998.