Overall and regional rates of norepinephrine overflow to plasma were measured in 55 untreated patients with primary hypertension and in 40 healthy subjects, to study sympathetic nervous pathophysiology in human hypertension. Total norepinephrine spillover was increased in primary hypertension, particularly in patients aged less than 40 years, largely due to higher rates of renal and cardiac norepinephrine overflow. Renal renin release, and arterial plasma renin activity, were highest in these younger patients with increased renal sympathetic nervous activity. In older patients sympathetic activity and norepinephrine release was typically normal. A selective increase in the sympathetic nervous outflow to the heart and kidneys is commonly present in young patients with primary hypertension, and probably contributes materially to the early pathogenesis of the hypertension.