We recently described a case of congenital dopamine beta-hydroxylase (DBH) deficiency. The syndrome is characterized by noradrenergic denervation, adrenomedullary failure, but intact baroreflex afferents, cholinergic innervation, and adrenocortical function. Norepinephrine, epinephrine, and their degradation products were undetectable in plasma, urine, and cerebrospinal fluid, whereas dopamine and its degradation products were elevated. Plasma DBH was not detectable. Studies in this novel syndrome showed evidence for the peripheral production of dopamine from sympathetic nerve terminals noradrenergic in nature. Tyrosine hydroxylase is probably induced in this syndrome, since plasma levels of L-DOPA were also elevated. Absence of hemodynamic effects of sympathicolytic agents in the face of an increase in blood pressure after dopamine antagonists suggest that intrasynaptic concentrations of dopamine are in the range of its plasma concentrations. Hypoprolactinemia, reduced REM sleep, increased slow wave sleep and sodium loss, despite low blood pressure, are further evidence for the biological role of dopamine in man.