To investigate the factors determining the natriuretic response to furosemide (F) during Na restriction, we performed clearance studies in 7 healthy humans on a daily Na intake of 200 and 20 mmol. The maximum urine flow during water loading (V<sub>max</sub>) and simultaneous F administration was used as index of tubular fluid output from the proximal tubules. The F-induced natriuresis was only moderately reduced during Na restriction (Na excretion on low vs. normal Na intake: 4.28 ± 0.25 vs. 4.94 ± 0.25 mmol/min; p < 0.05). The diminished natriuresis was mainly due to a significant fall in Na delivery to Henle’s loop of 0.51 ± 0.10 mmol/min which was either caused by a decrease in filtered Na load or a rise in fractional proximal reabsorption. Fractional distal Na reabsorption was less suppressible by F during Na restriction, but this contributed relatively little (0.15 ± 0.11 mmol/min) to the total reduction in Na excretion (0.66 ± 0.10 mmol/min). The F-induced increases in uric acid, phosphate, and bicarbonate excretion suggest an additional proximal site of action of F. This was confirmed by a rise in lithium clearance (C<sub>Li</sub>), another alleged index of tubular fluid delivery from the proximal tubules. However, the magnitude of the rise in C<sub>Li</sub> to values markedly exceeding V<sub>max</sub> suggest that C<sub>Li</sub> overestimates tubular fluid delivery to Henle’s loop during F administration.