F2-isoprostanes are prostaglandin-like compounds derived from free radical-catalysed peroxidation of arachidonic acid. Peroxidation of eicosapentaenoic acid produces F3-isoprostanes, whereas peroxidation of docosahexaenoic acid would give F4-isoprostanes. This study demonstrates the presence of esterified F4-isoprostanes in human brain and shows that levels are elevated in certain brain cortex regions in Alzheimer's disease. Our data with Alzheimer's disease suggest that analysis of F4-isoprostanes will provide new opportunities to study lipid peroxidation in the neurodegenerative diseases.