The hypothesis that substance P is the neurotransmitter of baro- and chemo-receptor nerve terminals synapsing in the nucleus tractus solitarius was tested by 1) measuring the content of substance P in four regions of NTS and in the sensory ganglia containing cell bodies of baro- and chemoreceptor afferents, and 2) determining the effect of intracranial sectioning of the rootlets of the IX and Xth nerves on the substance P content of the four regions of the NTS. Measurement of substance P in NTS and sensory ganglia revealed a high level of this material in parts of NTS where baro- and chemoreceptor afferents synapse and in nodose and petrosal ganglia. Denervation of cranial nerves IX and X of cats resulted in a 50 percent reduction of substance P content of parts of NTS where these afferents terminate, but no significant reduction in substance P content of parts of the NTS not involved in regulation of cardiovascular function.