To explore the role of dopaminergic mechanisms in orthostatic hypotension we compared the postural responses of 20 such patients to those of a control group by radioenzymatic determination of free and sulfated catecholamines and related indices. Patients with orthostatic hypotension, unlike control subjects, experienced an increase in total plasma dopamine (DA) (free + sulfate) in response to upright posture (p < 0.01). Of the 20 patients with orthostatic hypotension, 16 were normo- or hyperadrenergic with normal basal and posture-responsive or hyperresponsive plasma free and total norepinephrine (NE). The other 4 were hypoadrenergic with low basal and posture-unresponsive NE. Hypoadrenergic patients had, in the upright position, no increase in pulse rate and more severe hypotension, less diuresis and natriuresis, lower urinary free and total DA, lower total NE excretion, and higher plasma and urinary total DA:total NE ratio than normo- or hyperadrenergic patients or control subjects. Normo- or hyperadrenergic patients had higher PRA and plasma aldosterone in the upright position than hypoadrenergic patients or control subjects (all p < 0.05).We suggest that an excessive increase in free DA occurs in response to upright posture, perhaps representing a compensatory reaction of the remaining autonomic nervous system to an excessive fall in blood pressure. The free dopamine may be biologically active but it is so rapidly sulfoconjugated that it can be detected only as DA sulfate. These findings, combined with reports of orthostatic hypotension precipitated by administration of dopaminomimetic drugs and relieved by administration of dopaminergic antagonists, are consistent with the interpretation that excessive DA release may perpetuate, by its vasodilating and natriuretic action, the orthostatic hypotension.