Plasma catecholamines, hand-grip exercise and orthostatic stress were used to assess sympathetic nerve function in 14 hypertensive patients with mild to moderate renal failure and, for comparison, in 14 age-matched normal subjects. Furthermore, acute and chronic administrations of clonidine were used to determine a participation of the sympathetic nervous system in the maintenance of hypertension in these patients. Baseline mean blood pressure (MBP), plasma norepinephrine (NE), plasma renin activity (PRA) and aldosterone were elevated in patients with renal failure. During hand-grip exercise, the rise in MBP and in heart rate was blunted in these patients. During orthostasis, MBP decreased more while the increments in NE were greater in hypertensive patients that in normal subjects. Acute administration of clonidine (200 µg orally) resulted in a significant decrease in MBP, heart rate, NE, PRA, and aldosterone. There was a significant (p < 0.01) correlation between the decrease in NE and the fall in MBP. After 6 weeks of treatment, clonidine produced a significant decrease in MBP, heart rate, NE and aldosterone, but not in PRA. Chronic treatment with clonidine produced a slight but significant (p < 0.05) rise in serum potassium and in serum creatinine. Exchangeable sodium and plasma volume did not change significantly. The data indicate that abnormalities in the function of the sympathetic nervous system are already evident in patients with mild to moderate renal failure. The data also suggest that the sympathetic nervous system may participate in the maintenance of the hypertension in these patients.