Autonomic functions were evaluated in 25 nondialyzed patients with chronic renal failure and eight controls. Eight patients were reassessed after 6.6 ± 1.0 weeks of hemodialysis and 12 patients were restudied 24 ± 4.0 weeks after renal transplantation. In addition, six patients who had been on maintenance hemodialysis for a duration of 21.5 ± 3.0 weeks were also studied. Autonomic function tests, including blood pressure and heart rate response to sudden loud noise, mental arithmetic, hand immersion in cold water, Valsalva maneuver, change in posture and respiration, were performed using brachial artery cannulation and continuous monitoring by electrocardiogram. Baroreceptor sensitivity slope was determined using bolus injections of phenylephrine. Supine and standing plasma norepinephrine levels were measured. The cold pressor test, response to sudden loud noise and mental arithmetic were normal in nondialyzed patients with chronic renal failure, suggesting an intact efferent sympathetic pathway. The plasma norepinephrine concentration varied widely but the mean value was similar to the control group (P > 0.05). Expiration/ inspiration ratio, lying/standing ratio, Valsalva ratio and the baroreceptor sensitivity slope were significantly abnormal (P < 0.001) in nondialyzed patients. This indicates a defective efferent parasympathetic pathway and depressed baroreceptor sensitivity. The blood pressure response to phenylephrine was lower in the uremics, suggesting a reduced end-organ responsiveness to alpha agonists. The presence of hypertension did not affect autonomic function. The heart rate response to standing and the baroreceptor sensitivity were significantly lower (P < 0.05) in patients who developed hypotension during hemodialysis. Lower baroreflex sensitivity could contribute to hypotension during dialysis. Autonomic functions remained unaltered after short- and long-term dialysis. Following renal transplantation significant reversal of autonomic dysfunction was observed (P < 0.02).