Two cases of severe renal failure associated with the use of methoxyflurane anesthesia are reported. Both patients had polyuria during the immediate period after anesthesia and 7–10 days later became oliguric. After 26–31 days, a diuresis occurred with very slow recovery of adequate but reduced renal function. One case demonstrated hypernatremia and hyperosmolality. The development of renal failure did not depend upon a prolonged period of anesthesia. In one case, a renal biopsy revealed tubular epithelial cell degeneration, necrosis, and atrophy and crystals resembling calcium oxalate. Multiple mechanisms which may contribute to the development of renal failure associated with methoxyflurane are discussed. Supportive therapy, including dialysis, seems warranted to allow adequate time for return of renal function.