Vasopressin-resistant nonoliguric renal insufficiency developed in a 57-year-old man after 2 1/2 hours of low-dose methoxyflurane anesthesia. Secobarbital, 100 mg daily, had been taken for 1 month before. Of 13 patients in whom the influence of methoxyflurane on renal function was being studied, he was the only one to have taken a drug that induces microsomal enzymes. Blood values of methoxyflurane in this patient were lower than group means on all five occasions during anesthesia. Postoperatively his serum inorganic fluoride value reached 114 mumol/l -- more than two standard deviations greater than the group mean. Peak values for serum urea nitrogen, creatinine and uric acid and postvasopressin urine osmolality, and the lowest creatinine clearance in this patient also differed by more than 2 SD from the group mean, and the peak amount of oxalate excreted in his urine was double the group mean. Pretreatment with the barbiturate appears to have altered methoxyflurane metabolism and led to toxic concentrations of metabolites in the blood.