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The effects of anesthesia on ischemia-reperfusion injury are of considerable scientific and clinical interest. We examined the effects of propofol (known to possess antioxidant activity) and halothane (devoid of antioxidant activity in vitro) on tissue and red blood cell (RBC) antioxidant capacity. Adult male Wistar rats were anesthetized with halothane 0.5%–1.0% (n = 7), propofol 500 μg · kg−1 · min−1 with halothane 0.25%–0.5% (small-dose propofol;n = 9), or propofol 2000 μg · kg−1 · min−1 (large-dose propofol;n = 8) for 45 min. Blood and tissue samples of liver, kidney, heart, and lung were then harvested for in vitro exposure to a peroxidizing agent. Red cell malondialdehyde and tissue thiobarbituric acid reactive substances were determined spectrophotometrically. Antioxidant capacities of blood and tissues in the Large-Dose Propofol group, and of blood and all tissues except lung in the Small-Dose Propofol group, were increased significantly compared with halothane (P < 0.003). The increases in tissue antioxidant capacities varied in their magnitude: RBC > liver > kidney > heart > lung. There was a high correlation between changes in RBC susceptibility to oxidative damage and corresponding changes in tissues. These findings demonstrate that large-dose propofol significantly enhances tissue antioxidant capacity, and RBC antioxidant capacity can serve as a functional measure of tissue activity, in vivo.