The effects of the new diuretic metolazone were studied in ten patients with chronic renal insufficiency and ten with nephrotic syndrome. Patients were maintained on metolazone for up to 44 months. Beneficial effects of treatment included loss of edema and improved control of blood pressure. The natriuretic effect of metolazone facilitated the use of sodium bicarbonate to treat acidosis in several patients. Concurrent administration of metolazone and furosemide produced a dramatic diuresis in one patient resistant to either diuretic alone. Adverse effects of metolazone therapy were those characteristic of other effective diuretics, Including serum electrolyte losses and hyperuricemia. Initial treatment produced small increases in serum creatinine among patients with renal insufficiency, suggesting that GFR was decreased secondary to diuresis-induced volume depletion. The study demonstrates that metolazone is both safe and effective over long periods of time.