The human medulla contains catecholamine-and NADPH-diaphorase (NADPH-d) neurons in both the ventrolateral medulla (VLM) and nucleus of the solitary tract (NTS). There is abundant experimental evidence for the critical role of these areas in control of arterial pressure. We sought to determine the pattern of distribution and topographic relationship between tyrosine hydroxylase (TH)-immunoreactive and NADPH-d-reactive cell groups in normal human VLM and NTS, in view of their potential implications in human autonomic control and involvement in central autonomic disorders. Medullae from three patients with no neurologic disease were obtained at autopsy within 24 h of death. Individual sections, obtained from the rostral and caudal medulla, were stained for TH, NADPH-d or both. We found that: (1) TH-and NADPH-d positive neurons are topographically segregated in the VLM; (2) in the VLM, TH and NADPH-d neurons may coexist within a given area but both markers do not appear to coexist in single neuron; (3) NADPH-d-reactive fibers and processes overlap the distribution of TH neurons within the VLM; and (4) both TH-and NADPH-d-reactive processes appear to innervate intrinsic blood vessels in the VLM and NTS. Thus, there are important topographic relationships between catecholamine and NO-synthesizing neurons in human VLM and perhaps NTS, including innervation of intrinsic blood vessels. This may have important implications in regulation of autonomic reflexes, sympathetic excitatory drive and intrinsic control of cerebral blood flow in humans.