Sevoflurane is a recently introduced volatile inhalation anaesthetic and is already used commonly in Japan. We investigated the potential of sevoflurane to cause lipid peroxidation in vivo and in vitro. For the in vitro study, pentane formation in a mixture of guinea pig liver microsomes and sevoflurane in the presence of nicotinamide adenine dinucleotide phosphate (NADPH) was analyzed by gas chromatography. Under anaerobic conditions, pentane formed without sevoflurane, but sevoflurane potentiated this anaerobic pentane formation. Two antioxidant agents, vitamine E and glutathione, reduced the pentane formation induced by sevoflurane. In the in vivo study, 18 guinea pigs were exposed to air (control), 0.5% halothane, or 1.2% sevoflurane. The extent of lipid peroxidation and liver damage was investigated by measuring the level of thiobarbituric acid reactive products and serum transaminase (alanine-aminotransferase: ALAT and aspartate-aminotransferase: ASAT) activity 12 hr after exposure. Both halothane and sevoflurane significantly increased thiobarbituric acid-reactive products. The increase in thiobarbituric acid-reactive products seen with sevoflurane administration was half that seen with halothane. Sevoflurane increased the ALAT activity to the same extent as did halothane but did not increase the ASAT activity. We conclude that sevoflurane potentiates lipid peroxidation in guinea pig liver microsomes in vivo and in vitro. However, because the degree of liver damage as measured by transaminase activity was minimal and the mechanism of sevoflurane-induced lipid peroxidation is still unknown, we must be cautious in applying these results to humans.