Measurements of the overflow of norepinephrine to plasma from individual organs (using radiotracer methodology) were used to delineate the pattern of sympathetic nervous system activation present in primary human hypertension. Mean total norepinephrine (NE) spillover in hypertensive patients was 418 ng/min, 42% (124 ng/min) higher than in subjects with normal blood pressure (BP)(P less than .05). Norepinephrine spillover among hypertensive patients was a function of age, only being elevated in patients under 40 years of age. Half of the excess in total norepinephrine release in hypertensive patients was accounted for by increased cardiorenal spillover. Mean renal norepinephrine spillover was 120 ng/min, compared with 69 ng/min in healthy subjects (P less than .02). Renal spillover was highest in younger patients. Corresponding cardiac norepinephrine spillover values were 12.6 ng/min and 5.1 ng/min (P less than .01). The balance of the excess total norepinephrine spillover comes from undetermined sites, but not the lungs or hepatomesenteric circulation. These measurements of regional norepinephrine overflow suggest that sympathetic nervous outflow to the kidneys and heart is selectively activated in early hypertension.