Background: Volatile anesthetics protect against cardiac ischemia-reperfusion injury via adenosine triphosphate-dependent potassium channel activation. The authors questioned whether volatile anesthetics can also protect against renal ischemia-reperfusion injury and, if so, whether cellular adenosine triphosphate-dependent potassium channels, antiinflammatory effects of volatile anesthetics, or both are involved. Methods: Rats were anesthetized with equipotent doses of volatile anesthetics (desflurane, halothane, isoflurane, or sevoflurane) or injectable anesthetics (pentobarbital or ketamine) and subjected to 45 min of renal ischemia and 3 h of reperfusion during anesthesia. Results: Rats treated with volatile anesthetics had lower plasma creatinine and reduced renal necrosis 24 -72 h after injury compared with rats anesthetized with pentobarbital or ketamine. Twenty-four hours after injury, sevoflurane-, isoflurane-, or halothane-treated rats had creatinine (؎ SD) of 2.3 ؎ 0.7 mg/dl (n ؍ 12), 1.8 ؎ 0.5 mg/dl (n ؍ 6), and 2.4 ؎ 1.2 mg/dl (n ؍ 6), respectively, compared with rats treated with pentobarbital (5.8 ؎ 1.2 mg/dl, n ؍ 9) or ketamine (4.6 ؎ 1.2 mg/dl, n ؍ 8). Among the volatile anesthetics, desflurane demonstrated the least reduction in plasma creatinine after 24 h (4.1 ؎ 0.8 mg/dl, n ؍ 12). Renal cortices from volatile anesthetictreated rats demonstrated reduced expression of intercellular adhesion molecule 1 protein and messenger RNA as well as messenger RNAs encoding proinflammatory cytokines and chemokines. Volatile anesthetic treatment reduced renal cortex myeloperoxidase activity and reduced nuclear translocation of proinflammatory nuclear factor B. Adenosine triphosphatedependent potassium channels are not involved in sevofluranemediated renal protection because glibenclamide did not block renal protection (creatinine: 2.4 ؎ 0.4 mg/dl, n ؍ 3). Conclusion: Some volatile anesthetics confer profound protection against renal ischemia-reperfusion injury compared with pentobarbital or ketamine anesthesia by attenuating inflammation. These findings may have significant clinical implications for anesthesiologists regarding the choice of volatil