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 (Vmax) 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 (CLi), another alleged index of tubular fluid delivery from the proximal tubules. However, the magnitude of the rise in CLi to values markedly exceeding Vmax suggest that CLi overestimates tubular fluid delivery to Henle’s loop during F administration.