Patients with autonomic failure provide a unique opportunity to study the role of sympathetic function on the regulation of blood volume. These patients have a reversal of the normal diurnal variation in urine output and have twice as much natriuresis during the night. Autonomic failure patients are also unable to conserve sodium and fail to decrease natriuresis in response to dietary sodium restriction. Whereas normal subjects are able to maintain blood pressure within narrow values throughout a wide range of plasma volumes, blood pressure is linearly correlated to changes in plasma volume in autonomic failure patients. Fludrocortisone is often used to increase plasma volume in these patients, but this effect is only transient; its long-term effectiveness probably is due to potentiation of the pressor effects of norepinephrine. On the other hand, epoetin-alpha is effective in correcting the mild anemia that autonomic failure patients commonly have and improves their orthostatic hypotension in part by increasing intravascular volume. Autonomic failure patients, therefore, illustrate the role the sympathetic nervous system has in the regulation of sodium and volume. Conversely, a high salt diet induces sympathoinhibition in normal subjects. Paradoxically, sympathetic activity is increased in patients with salt-sensitive hypertension and contributes to their increase in blood pressure. Thus, in both these conditions the feedback mechanisms involving the sympathetic nervous system and volume homeostasis are impaired.