The cell membrane is protected against lipid peroxidation through endogenous antioxidants such as the lipid soluble alpha-tocopherol. The anesthetic agent propofol (2,6-diisopropylphenol) has a chemical structure which is similar to alpha-tocopherol, since it also contains a phenolic OH-group. The transient protection of GSH against lipid peroxidation in control liver microsomes is not observed in microsomes deficient in alpha-tocopherol. Introducing propofol (2 and 5 microM) restored the protective effect of GSH. Similar to the control microsomes the GSH-protective effect did not occur in previously heated microsomes. These results suggest that propofol acts similarly to alpha-tocopherol as a chain breaking antioxidant in liver microsomal membranes.