Normal subjects given propranolol increased their plasma t1/2 for infused isoproterenol from 2.68 to 6.25 minutes. Propranolol increased plasma norepinephrine (NE) levels only slightly. Propranolol increased the t1/2 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. alpha-Blockers slow uptake-1 and beta-blockers slow uptake-2 processes. When 27 subjects exercised, those who attained the highest plasma levels of the alpha- and beta-receptor agonist NE also had the briefest apparent t1/2 for NE. Adrenergic receptor blocking drugs slow catecholamine clearance. NE may stimulate its own clearance.