Diuretic-induced magnesium losses may contribute significantly to magnesium deficiency. Loop diuretics especially cause major losses of urinary magnesium. Our initial experiments in saline-loaded rats indicated that frusemide greatly increased magnesium excretion, while bendrofluazide caused no significant change and triamterene actually decreased magnesium excretion. Therefore, not all diuretics are magnesium-wasting. There is evidence that the potassium-sparing diuretic amiloride may also exert magnesium-sparing properties. In saline-loaded rats, the magnesium-sparing effect of amiloride was demonstrated when the drug was administered either alone or in combination with frusemide. Renal clearance studies in rats indicated that the magnesium-sparing effect of amiloride was a direct renal action and not secondary to possible extrarenal actions. A dose-response relationship has been established for the effect of amiloride in reducing fractional excretion of magnesium and potassium during frusemide diuresis in rats. Congestive heart failure patients being treated with frusemide were found to be both potassium- and magnesium-deficient, as indicated by reduced lymphocyte concentrations of potassium and magnesium. In these patients, amiloride reduced urinary magnesium and potassium, increased plasma magnesium and potassium, and also increased lymphocyte magnesium and potassium. The effects of amiloride most likely involve enhanced reabsorption of magnesium, but further studies are required to establish the precise mechanism(s) involved in the drug's magnesium-sparing properties.