It has been postulated that delayed facilitation of norepinephrine release by epinephrine is causally related to the development of hypertension. It has been proposed that a brief increase in epinephrine concentrations results in the uptake of epinephrine into the sympathetic nerve terminal. Subsequent rerelease of epinephrine stimulates presynaptic beta-adrenergic receptors, resulting in a prolonged increase in plasma norepinephrine (NE) concentrations, with amplified sympathetic responses and vasoconstriction. To determine whether such epinephrine-induced, delayed facilitation of NE release occurs in a vascular bed draining resistance vessels and, if it occurs, whether that facilitation differs in hypertension, we used a radioisotope dilution method to measure unstimulated and isoproterenol-stimulated forearm NE spillover before, during, and after a 50 ng/min infusion of epinephrine for 30 minutes directly into the brachial artery. No delayed facilitatory effects of epinephrine on forearm NE spillover were observed in either 6 normotensive (NT) or 8 borderline hypertensive (BHT) subjects (NT unstimulated forearm NE spillover preepinephrine 1.79+/-0.41 ng/min versus postepinephrine 2.36+/-0.65 ng/min, P=.38; BHT preepinephrine 2.24+/-0.70 ng/min versus postepinephrine 1.93+/-0.46 ng/min, P=.51; NT isoproterenol-stimulated forearm NE spillover preepinephrine 4.61+/-1.01 ng/min versus postepinephrine 4.4+/-0.98 ng/min, P=.9; BHT preepinephrine 4.04+/-1.36 ng/min versus postepinephrine 4.69+/-1.49 ng/min P=.5). We conclude that the short-term local infusion of epinephrine does not have a delayed facilitatory effect on forearm NE spillover in NT or BHT subjects. Therefore, the prolonged increase in NE concentrations after epinephrine infusion previously shown systemically, and not seen locally in the forearm, suggests that the delayed facilitatory response to epinephrine may occur in other organs.