An acidotic state has been shown to inhibit sodium (Na) transport both in vitro in toad and turtle bladders an in vivo in rat and dog proximal tubules. To determine if renal Na transport was altered in man by acidosis, we examined the effect of metabolic acidosis produced by ammonium chloride (NH<sub>4</sub>CI) ingestion on proximal and distal tubular Na reabsorption under conditions of maximal water diuresis in seven normal volunteers. During maximal water diuresis, urinary volume (V) can be used as an estimate of Na and H<sub>2</sub>O delivered out of proximal tubule, the clearances of free water and sodium (CH<sub>2</sub>O + CNa) as an estimate of distal Na delivery, and the clearance of free water (CH<sub>2</sub>O) as a measure of Na reabsorption in the diluting segment. The urinary volume, the distal Na delivery, and the clearance of free water were not significantly different in the control (HCO<sub>3</sub> – 24.6 mEq/l, venous pH 7.34) and experimental (HCO<sub>3</sub> – 15.9 mEq/l, venous pH 7.25) states. However, the proportion of Na load reabsorbed by the diluting segment CH<sub>2</sub>OCH<sub>2</sub>O±CNa×100 Can was higher in the acidotic state (p < 0.01). It is concluded that moderate metabolic acidosis does not affect proximal Na reabsorption in man. An increased fractional reabsorption of Na distally is seen in acidosis and may reflect a direct effect of metabolic acidosis on the diluting segment or be secondary to the greater chloride and lesser bicarbonate presented to the diluting segment during acidosis.