The effects of graded infusions of the β-agonists isoproterenol (nonselective), l-prenalterol β1-selective), and salbutamol (β2-selective) on plasma potassium and norepinephrine were compared in subjects with borderline hypertension. Potassium levels fell with all three agonists, and norepinephrine levels rose with isoproterenol and salbutamol. These effects on potassium and norepinephrine were closely correlated and occurred at the same dose ranges as the cardiovascular responses. The fall in plasma potassium was probably caused by activation of β-receptors, mainly on skeletal muscle, with subsequent stimulation of active sodium-potassium transport across the cellular membrane. The rise in plasma norepinephrine may have been due to activation of β-receptors on sympathetic nerve endings. Activation of these presynaptic receptors is known to enhance the release of norepinephrine during nerve stimulation. For a given increase in heart rate and cardiac contractility, as measured by the heart rate-corrected duration of total electromechanical systole, which are mainly β1-responses, the effects on potassium and norepinephrine were in the order: salbutamol > isoproterenol > prenalterol. β-Blockade with propranolol (nonselective), 80 mg four times a day, or atenolol (β1-selective), 100 mg once a day, antagonized the hypokalemic effect of isoproterenol as well as the rise in norepinephrine, but when isoproterenol was infused in doses high enough to overcome the blockade of the heart rate response, the effects on norepinephrine and potassium were abolished by propranolol and not by atenolol. Thus, the receptors in question appear to be of the β2-subtype. Epinephrine, which is known to circulate in high concentrations under stressful conditions, is generally considered to be the endogenous activator of these receptors. β-Blockers may prevent hypokalemia and may suppress sympathetic activity, which could contribute to their so-called cardioprotective action. The evidence presented here and in other studies that β2-type receptors are involved in stress-induced hypokalemia and in presynaptic facilitation of norepinephrine release warrants further consideration of the clinical significance of β-blocker selectivity.