FERRITIN contains most of the iron found in the brain, and the release of iron from ferritin has an essential role in iron-dependent lipid peroxidation. We examined the effect of cultured microglia on the ferritin-dependent lipid peroxidation of phospholipid liposomes monitored by the formation of thiobarbituric acid-reactive substances. Microglia stimulated by phorbol myristate acetate caused lipid peroxidation in the presence of ferritin. This lipid peroxidation was mediated by super-oxide produced by the microglia and iron released from the ferritin. Lipid peroxidation induced by activated microglia may be partly responsible for the oxidative damage that is thought to occur in Parkinson's disease and other neurodegenerative disorders.