Background: Rats with chronic renal failure have a low nitric oxide (NO) production and a diminished NO excretion. The supplementation of L-arginine has an inhibitory effect on the progression of renal insufficiency. Methods: The present study was designed to determine whether chronic renal failure patients have a low NO production. Plasma and urine nitrate (NO<sub>3</sub>) and nitrite (NO<sub>2</sub>), stable metabolites of NO, were measured in 83 consecutive patients with chronic renal failure. The 83 chronic renal failure patients were divided into three groups: group 1, mild renal failure (creatinine clearance >60 ml/min/1.73 m<sup>2</sup>); group 2, moderate renal failure (creatinine clearance >30 <60 ml/min/1.73 m<sup>2</sup>), and group 3, severe renal failure (creatinine clearance <30 ml/min/1.73 m<sup>2</sup>). Thirty-three healthy volunteers served as controls. Results: The daily urinary NO excretion was significantly lower in patients with moderate and severe renal failure as compared with those with mild renal failure and normal controls. The lowest values were found in the severe renal failure group. When the 24-hour urinary NO excretion or NO per milligram creatinine and the NO clearance were correlated with the renal function in all patients as a group, these parameters were directly correlated with the creatinine clearance and inversely correlated with the serum creatinine level. The plasma NO concentration was not different between the three chronic renal failure groups, but higher than in the controls. Plasma NO in renal failure patients was not correlated with the creatinine clearance or serum creatinine levels. Conclusions: Chronic renal failure is a state of NO deficiency. Treatment strategies to increase NO production ( L-arginine supplementation or other NO compounds) may prove to be useful in maintaining the renal function and slow the progression of renal disease.