Metolazone, a new diuretic agent, was administered to patients with ascites and edema. After injection of a single dose, natriuresis, diuresis, and kaliuresis began promptly and persisted for two to three days. This uniquely prolonged duration of action is attributable to avid protein-binding and enterohepatic recycling of the drug, which result in slow disappearance from the body. In three of four responsive patients potassium excretions increased only slightly, despite moderately large increases in sodium excretion. Three other patients who were resistant to metolazone demonstrated kaliuresis even though the daily rate of sodium excretion increased by only a few milliequivalents. Metolazone appears to be a clinically useful diuretic agent which continues to act for an unusually long time after administration of a single dose. During metolazone therapy, natriuresis and kaliuresis may occur independently of each other.