To evaluate the validity of the lithium clearance method as a marker of overall proximal tubular fluid delivery in moderately sodium-depleted humans, the effects of a single dose of 10 mg amiloride on lithium clearance and glomerular filtration-rate were studied in normal volunteers maintained on a sodium diet of 50 mmol/day. Amiloride caused no changes of the glomerular filtration-rate or of lithium clearance. The effects of amiloride on tubular sodium, potassium and water handling were in accordance with a distal tubular action of amiloride. The results suggest that significant distal lithium reabsorption does not occur in measurable amounts during moderate sodium depletion in humans. The lithium clearance method may, therefore, be used to assess proximal fluid delivery in man when dietary sodium intake is as low as in the present study.