Sevoflurane, 3% and 4% in oxygen was administered to four dogs for 3 hours. Sevoflurane was metabolized to inorganic fluoride and hexafluoroisopropanol. Serum fluoride concentrations reached peak values during 2 to 3 hours into anesthesia and averaged 18.5 micrometer/L (n = 2) and 20.0 +/- 4.8 (mean +/- SD) micrometer/L (n = 4) following 3% and 4% sevoflurane exposure, respectively. They returned to normal values within 24 hours after anesthesia. Hexafluoroisopropanol was excreted in the urine as glucuronide conjugate. Its elimination was essentially complete within 48 hours after the end of exposure to sevoflurane. During inhalation of 4% sevoflurane, blood concentration of the anesthetic reached an average apparent steady state of 0.765 +/- 0.10 micrometer/L (n = 4). No anesthetic was detected in blood 24 hours after this exposure. Rats were anesthetized with 2% sevoflurane for 2 and 4 hours. Immediately after anesthesia, observed mean (n = 6) serum fluoride concentrations were 2.9 +/- 0.5 micrometer/L and 2.5 +/- 0.6 micrometer/L, respectively. Hepatic microsomal enzyme induction produced by pretreatment with either phenobarbital or polychlorinated biphenyls (PCBs) resulted in an approximately 5-fold increase in serum fluoride concentrations following anesthesia with sevoflurane when compared to noninduced rats exposed to sevoflurane. A comparison of serum fluoride concentrations between the rat and dog indicates that the amount of sevoflurane metabolized is lower in the rat than in the dog, and the fluoride concentrations observed in both animal species during sevoflurane anesthesia are not expected to produce nephrotoxicity.