Metolazone, a new diuretic/saluretic/anti-hypertensive agent related to quinethazone, was used to treat 20 patients with impaired renal function. Among eight water loaded hospitalized patients given metolazone 5 mg intra venously, glomerular filtration rate rose in four and diminished slightly in four while urine flow and sodium excretion in creased significantly. In 12 out-patients given long-term oral metolazone (usually 5–10 mg in single daily doses) treatment effectively removed oedema and induced weight loss; in the seven initially hypertensive patients blood pressure decreased also. Plasma renin activity was measured in seven patients before and after several weeks’ metolazone therapy. Activity fell in two patients and rose in five, but the upper limit of normal was exceeded in one only. Renal epithelial cell excretion rates indicated that drug nephrotoxicity was absent. Mean creatinine clearances rose, serum potassium levels fell, and ten patients received oral potassium supplements. Small transient increases in liver enzymes were seen in three patients. Metolazone tended to maintain glomerular filtration rate and renal plasma flow while increasing salt and water losses. A proximal as well as a distal site of action was suggested for the drug, and its anti-hypertensive effect was confir