Clearance techniques were used to evaluate renal tubular sodium and water excretion in 4 patients with antibiotic-induced acute renal failure (ARF). Creatinine clearances and maximal urine flow rates of patients with ARF (22.6 and 5.23 ml/min, respectively) were significantly lower than control values during hypotonic volume expansion (125.5 and 13.71 ml/min, respectively, both p < 0.01). During the period of maximal hydration, fractional sodium excretion (CNa/Ccr) and maximal urine osmolality (11.4% and 171 mosm/kg H<sub>2</sub>O, respectively) were increased compared to controls (1.04% and 53 mosm/kg H<sub>2</sub>O, respectively, both p < 0.05). The increased C<sub>Na</sub>/C<sub>cr</sub> observed in patients with ARF was consistent with reduced proximal sodium reabsorption as reflected by increased (C<sub>H2 O</sub> + C<sub>Na</sub>)/C<sub>Cr</sub> and reduced fractional distal sodium reabsorption as indicated by decreased C<sub>H2 O</sub>/(C<sub>H2 O</sub> + C<sub>Na</sub>). The reduction in proximal and distal sodium reabsorption cannot be explained on the basis of an osmotic effect of urea as fractional clearances of BUN (C<sub>bun</sub>/c<sub>cr</sub>) were similar in patients with ARF and controls.