The acute effects on potassium excretion of the new diuretic agent, metolazone, were compared to those of chlorothiazide, acetazolamide, furosemide, and ethacrynic acid. Metolazone was antikaliuretic when mildly natriuretic, nonkaliuretic when modestly natriuretic, and only minimally kaliuretic at the highest rates of sodium excretion obtained (apprOXimately 5% to 7% of filtered load). This action of the drug on potassium excretion was not obviated by superimposing its administration on steady‐state ethacrynic acid diuresis, but the provision of pharmacologic doses of mineralocorticoid did convert it to a frankly kaliuretic agent. In comparison to the other diuretics, metolazone showed the least tendency to induce urinary potassium loss, but ethacrynic acid was also nonkaliuretic at low levels of natriuresis. Both metolazone and ethacrynic acid were much less kaliuretic than the carbonic anhydrase inhibitors: acetazolamide, furosemide, and chlorothiazide.