: 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.