We speculated that the inhibitory effect of isoflurane on the metabolism of halothane might reduce hepatic injury produced by halothane. To test tliis hypothesis we pretreated male rats with phenobarbital and 24 hr later exposed them to one of three types of anesthesia. One group of rats was anesthetized with 0.6 MAC isofliirane in 21–25% oxygen for 20 min, followed by exposure to 0.3 MAC isofliirane and 0.3 MAC halothane either in 9% oxygen for 46 min (n = 5) or in 12% oxygen for 60 min (n = 11). A second group of rats received 0.3 MAC halothane in 9% oxygen for either 46 min (n = 12) or in 12% oxygen for 60 min (n = 10). The third group received 0.3 MAC isoflurane in 9% oxygen for either 46 min (n = 12) or for 120 min (n = 8). The rats were killed 24 hr after the exposures and liver slides prepared. Histologic examination revealed that rats treated with isoflurane plus halothane, or with halothane alone showed a significant hepatic injury (P < 0.005) when compared with those treated with isoflurane. Thus isoflurane failed to protect the liver from halothane-induced injury.