Plasma norepinephrine derives from sympathetic nerves, but the proportion reaching the circulation before being metabolized varies with the type of nerve ending-effector junctions in the tissue. Plasma levels of norepinephrine also will fluctuate because of rapid metabolism rates and environmental, emotional, and endogenous stimuli provoking a sympathetic response. The responses of plasma catecholamines in spontaneously hypertensive rats and in normotensive rats of the same strain were compared after exposure to a variety of stressors. Drugs that inhibit monoamine oxidase, catechol-O-methyl transferase, or neuronal uptake were administered to show the effects of metabolic enzymes and neuronal uptake on the amounts of catecholamines reaching the circulation. Sympathetic nervous activity and the ability of the sympathetic nervous system to respond to a uniform stimulus are studied in hypertensive and normotensive subjects. A survey of the plasma levels of norepinephrine in a variety of neurologic disorders is given.