SUMMARY To gain insight into the factors involved in the maintenance of sodium balance in patients with chronic renal failure, we studied 10 patients with a creatinine clearance of 11.5 ± 4.0 ml/min after equilibrium on 20 and 120 mEq of sodium per day. The measurements included blood pressure, plasma volume, blood volume, extracellular fluid volume, plasma renin activity, plasma aldosterone, and plasma norepinephrine. For comparison, eight normal volunteers were studied after equilibration on 20, 200, and 1128 mEq of sodium per day. The latter intake was chosen to match the high sodium intake per residual renal function in the patients. In the patients, equilibrium after raised sodium intake was accompanied by a marked increase in blood pressure and blood volume, a moderate fall in plasma renin activity and levels of aldosterone and norepinephrine, and only little expansion of the interstitial space. The 24-hour creatinine clearance rose by 21.2 ± 7.2%. Fractional sodium excretion (x 100%) was 5.3 ± 0.8% during the 120 mEq sodium diet. In the normal volunteers, increasing the sodium intake from 20 to 1128 mEq/day evoked no consistent change in blood pressure but caused a comparable rise in blood volume, considerable suppression of plasma renin activity, aldosterone, and norepinephrine, and a much larger increase in interstitial volume. Their creatinine clearance had risen by 22.4 ± 6.5%, and their fractional sodium excretion during the 1128 mEq sodium intake was 3.9 ± 0.2%. These results suggest that in normal subjects the maintenance of sodium balance over a wide range of sodium intake is particularly dependent on variations of neurohumoral influences on the kidney, while in patients with renal failure relatively large variations in arterial pressure are necessary as well. The marked difference in amount and distribution of the retained volume may be explained by a vasoconstrictive reaction to sodium loading in the patient group. (Hypertension 7: 714-721, 1985) KEY WORDS volume sodium loading renin • aldosterone hypertension • norepinephrine blood volume extracellular fluid