Certain anesthetics have been suggested to protect against the pathological states associated with oxidative stress. We compared the antioxidant and membrane activities of propofol (2,6-diisopropylphenol) and its related compounds to address the structure-activity relationship especially in a lipid membrane phase. They were studied for the effects on 1,1-diphenyl-2-picrylhydrazyl radicals, nitro blue tetrazolium reduction by superoxide anions and membrane lipid peroxidation by peroxynitrite, and also for the induced changes in membrane fluidity of liposomes. 2-Isopropylphenols scavenged free radicals with the potency being propofol>2,5-diisopropylphenol>2-isopropylphenol>2,4-diisopropylphenol, but not 3- and 4-isopropylphenols and 1,3- and 1,4-diisopropylbenzenes. The tested compounds showed no significant superoxide dismutase-like effects. Propofol inhibited membrane lipid peroxidation more intensively than 2,5-diisopropylphenol, 2,4-diisopropylphenol and 2-isopropylphenol. Despite structurally resembling antioxidant alpha-tocopherol, 2,6-dimethylphenol was less potent than propofol. Propofol produced 50% inhibition of the lipid peroxidation in unsaturated phosphatidylcholine liposomal membranes and cell-mimetic membranes at 4.0 and 10.1 microM, respectively. Propofol and 2-alkylphenolic compounds interacted with membranes to increase their fluidity with the potency correlating with lipid peroxidation inhibiting activity. The 2-isopropylphenol structure is a requisite for both lipid peroxidation inhibition and membrane fluidity modification. The structure-specific membrane interactivity appears to be one of possible antioxidant mechanisms for propofol.