Although catecholamines are rapidly removed from the extracellular fluid, the role of adrenergic mechanisms in the clearance of epinephrine and norepinephrine has not been defined. In five normal human subjects, mean (+/- SE) plasma epinephrine concentrations did not change during control infusions, rose from 21 +/- 6 pg/ml to 834 +/- 84 pg/ml during the infusion of epinephrine (50 ng/kg/min) over 180 min and to 853 +/- 112 pg/ml during the infusion of epinephrine plus phentolamine (500 micrograms/min after a 5.0 mg loading dose infused over 2 min), but to 2400 +/- 104 pg/ml during the infusion of epinephrine plus propranolol (80 micrograms/min after a 5.0 mg loading dose infused over 2 min), indicating that beta-adrenergic blockade sharply reduces the clearance of epinephrine in man. In separate studies in seven subjects, similar increments in plasma epinephrine occurred during the infusion of epinephrine alone and the clearance of epinephrine was comparably reduced during the infusion of epinephrine plus propranolol and during the infusion of epinephrine plus propranolol plus phentolamine, suggesting that the reduction of epinephrine clearance produced by beta-adrenergic blockade during epinephrine infusion is not mediated by an alpha-adrenergic reduction of blood flow to organs of epinephrine clearance. Endogenous plasma norepinephrine concentrations doubled during the infusion of phentolamine without propranolol but rose to nearly fourfold higher values during the infusion of phentolamine with propranolol indicating that beta-adrenergic blockade reduces the clearance of norepinephrine as well as that of epinephrine. These findings indicate that epinephrine and norepinephrine are cleared through beta-adrenergic, but not alpha-adrenergic, mechanisms in man.