Three weeks after dosing male Fischer 344 rats with streptozotocin to induce diabetes, enflurane was administered ip, and 1 h later, fluoride levels were measured in plasma and livers were removed. Hepatic microsomes were prepared, and the oxidative defluorination of enflurane, isoflurane, and methoxyflurane and the reductive defluorination of halothane were measuredin vitro.In diabetic rats the defluorination of enflurane was increased 3.4-fold over control levelsin vivoand 2.7-foldin vitro.Insulin treatment prevented these effects. In vitro, metabolism of isoflurane by livers from diabetic rats was 2.5-fold greater than by livers from control rats, but defluorination of methoxyflurane and of halothane was not altered. The results show that streptozotocin-induced diabetes in rats enhances the defluorination of enflurane and of isoflurane but not of methoxyflurane or halothane.