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Among 94 cases in which methoxyflurane was used, 16 developed a toxic nephropathy characterized by diuresis. A seventeenth case which occurred 2 years previously in an affiliated hospital is also reported. Variations in the severity and duration of water loss modified the clinical features which, in which, well-defined cases, consisted of: urine volume of 2.5 to 4 liters per day with a negative fluid balance and pronounced weight loss for 6 to 10 days; elevation of serum sodium, chloride, osmolality and blood urea nitrogen; a relatively fixed urine specific gravity; urine osmolality in a range close to that of the serum and poorly responsive to a challenge test of fluid deprivation, rapid infusion and Pitressin. In most cases renal functional impairment was transient (10–20 days), but in 3 cases an elevated blood urea nitrogen remained 12, 16 and 29 months after onset.