Normal subjects given propranolol increased their plasma t 1 2 for infused isoproterenol from 2.68 to 6.25 minutes. Propranolol increased plasma norepinephrine (NE) levels only slightly. Propranolol increased the t 1 2 of isoproterenol but not that of NE in men with autonomic nervous system degeneration. This suggests that propranolol acts on nonneuronal uptake-2 processes, rather than on uptake-1 mechanisms. α-Blockers slow uptake-1 and β-blockers slow uptake-2 processes. When 27 subjects exercised, those who attained the highest plasma levels of the α- and β-receptor agonist NE also had the briefest apparent t 1 2 for NE. Adrenergic receptor blocking drugs slow catecholamine clearance. NE may stimulate its own clearance.