We studied the efficacy of long loop diuretics in the treatment of hyponatremia associated with inappropriate secretion of antidiuretic hormone (SIADH) in 12 patients, and in 2 healthy volunteers with Pitressin®-induced SIADH. In the 2 volunteers and in all but 1 patient, the serum sodium concentration was normalized by furosemide or ethacrynic acid despite free access to water, but provided salt intake was high enough to compensate for the urinary sodium losses. The patient who did not respond had only a slight increase in his diuresis after 40 mg of furosemide, probably because creatinine clearance was initially low (44–55 ml/min). He achieved a good control with urea. The usual diuretic dose was 40 mg furosemide or 50 mg ethacrynic acid/day; only 2 patients required higher doses, 80 mg furosemide and 100 mg ethacrynic acid, respectively. Supplementary salt in tablets (3–6 g daily) had to be administered to 9 of the 11 responding patients. Hypokalemia developed in 7 patients but was easily corrected either by KCl supplements (30–40 mmol/day) in 3 patients, or triamterene administration (50 mg/day) in the remaining 4. It is concluded that treatment with long loop diuretics is a valuable alternative for the treatment of patients with SIADH syndrome in whom hyponatremia persists despite acceptable water restriction. Long loop diuretics are likely to be preferable to urea if urine osmolality and creatinine clearance are high, since a high-urea dose should then be necessary to obtain a sufficiently osmotic diuresis. On the contrary, urea will be the preferred drug if creatinine clearance is relatively low and urine osmolality is lo