Thiazides and amiloride are the most often suggested treatment for nephrogenic diabetic insipidus. We found this ineffectual in a patient with acute problems and reviewed the literature to see if there were other more efficient approaches. A 47-year-old woman on lithium had polyuria. When inadvertently fasted for 48 h she became confused, had a seizure, and her sodium was 170 mmol/L. Urinary output was 24 L/day. Large volumes of intravenous fluids were given but sodium remained > 170 mmol/L. Treatment with DDAVP, thiazides, and amiloride did not decrease urinary output. Indomethacin 150 mg was started and urine volume immediately fell to one-half. However, because of persistent high urine output the patient was then fluid depleted, with further reduction to normal in urine volume, and Na decreased to 140 mmol/L. Creatinine rose from 135 mumol/L to 173 mumol/L, but decreased to 152 mumol/L when indomethacin was decreased to 75 mg q.d.; urinary output remained stable around 2 L/day. The literature described 22 patients with nephrogenic diabetes insipidus (16 congenital, 6 lithium) treated with nonsteroidal anti-inflammatory drugs. Urine flow was reduced to 1/3, within hours. Rarely, mild renal failure ensued, improving in all but one case when nonsteroidal anti-inflammatory drugs were reduced. Indomethacin (and controlled volume reduction if continued high urine output), while observing renal function, appears the emergency treatment of choice for serious complications of nephrogenic diabetes insipidus.