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In 1936 hemodynamic measurements in patients with essential hypertension suggested the presence of a functional increase in peripheral vasoconstriction producing an abnormally high peripheral resistance to blood flow (1). The concept that physiologic degrees of vasoconstriction were maintained by the adrenergic neurohumor, norepinephrine (NE), was proposed almost simultaneously (2), but it was nearly 10 years later that von Euler (3, 4), Holtz, Credner, and Kroneberg (5), and others demonstrated that NE was normally present in and released by mammalian sympathetic nerves. Within a year, Goldenberg and co-workers (6) suggested that essential hypertension might be caused by the simple overproduction of NE. This neurohumoral theory underwent repeated evaluation, first by the measurement of NE in urine (7, 8) and plasma (9), and later by the assay in urine of the major NE catabolites, vanillylmandelic acid (VMA) (10), normetanephrine (NM) (11), and 3-methoxy, 4-hydroxyphenyl glycol (NMG) (12).Since no clear-cut evidence of NE overproduction could be found (8-10), and since physiologic studies suggested that essential hypertension was associated with abnormally increased vascular reactivity to infused NE (13), it seemed possible that the disease might be causally related to abnormal metabolic handling of that NE produced in normal quantities by these patients. To evaluate the metabolism of a substance that underwent degradation within moments of its administration and which produced an intense physiologic effect in nanogram amounts, a tracer compound of high