To evaluate the activity of the sympathetic nervous system in chronic renal failure, plasma norepinephrine (NE) and dopamine-beta-hydroxylase (DBH) activity were measured by a radioenzymatic assay and a photometric assay respectively. The level of plasma NE was significantly higher in 14 patients with hemodialysis than in healthy individuals (p less than 0.001). The level of plasma NE fell significantly in 6 patients with hemodialysis receiving 0.30-0.45 mg/day of clonidine hydrochloride (a depressor of the sympathetic outflow from the central nervous system) (p less than 0.05). Systolic blood pressure was correlated with the level of plasma NE in patients with hemodialysis who were not receiving clonidine. They had high level of plasma NE and low level of plasma DBH activity. Therefore, this findings suggest that high level of plasma NE in chronic renal failure is caused not only by decreased urinary excretion, but also by increased overflow from the sympathetic nervous clefts.