Plasma norepinephrine (NE) levels are normal or elevated in patients with renal failure even though uremia often damages the sympathetic nerves that release NE. We infused 3H-NE into subjects with normal, mildly depressed, or absent renal function. 3H-NE clearance was depressed 20% in mild renal failure and 40% in patients on hemodialysis. The calculated rate of NE release into plasma was low in uremics even though their plasma NE was normal. Dopamine beta hydroxylase (D beta H) and chromogranin A are released from sympathetic nerve endings along with NE. D beta H levels were low in uremia and D beta H levels doubled following hemodialysis. Chromogranin A levels were very high in uremics and increased slightly following hemodialysis. Plasma clearance of both NE and chromogranin A appears low in renal failure. The calculated rate of NE release is diminished in uremics, which is in accord with reports of autonomic neuropathy in these patients.