The renal response to a single intravenous dose of ethacrynic acid was evaluated in ten patients with cardiac decompensation. Following infusion of the drug, a prompt increase in urine flow occurred lasting for approximately two hours. During this diuresis, renal function studies disclosed a fall in tubular reabsorption of water, sodium and chloride, and an increase in osmolar clearance. These findings are compatible with a blockade of coupled sodium chloride reabsorption in either the ascending loop of Henle or early distal tubule or both, but do not exclude a redistribution of intrarenal blood flow as contributing significantly to ethacrynic acid's mode of action. Distal tubular exchange between sodium and potassium-hydrogen does not seem to be affected by this diuretic.