The relationship of natriuretic effect and furosemide excretion was studied in normal and azotemic dogs. Graded azotemia was produced in dogs by bilateral uretero-venous shunts of varying duration. The shunts were subsequently opened and urine and blood samples were taken to measure inulin, furosemide and sodium concentrations. Renal blood flow was measured by an electromagnetic flow probe. Two groups of dogs, control and experimental, were studied. The experimental group received a loading dose followed by a constant infusion of furosemide. This dose produced a natriuresis in nonazotemic normal dogs. The magnitude of this natriuresis correlated with furosemide excretion rate (P less than .005) and not with the plasma concentration of the drug. Furosemide clearance and extraction were inversely correlated with blood urea nitrogen. In the furosemide-treated group the augmentation of sodium excretion was not impaired except at blood urea nitrogen concentrations of greater than 200 mg/dl (two dogs). Thus the reduced clearance of furosemide may account in part for the high dose necessary. Further studies appear to be in order to clarify the relationship of the natriuretic response to furosemide to the rate of urinary excretion and plasma concentration of the drug.