We evaluated the role of iron in the toxicity of oxidized low density lipoprotein (Ox-LDL) to cultured vascular endothelial cells. Exposure of the endothelial cells to Ox-LDL led to cell lysis as judged by the release of lactate dehydrogenase into the medium. The presence of deferoxamine, an iron chelator, in the reaction medium containing Ox-LDL prevented the lysis of cells by Ox-LDL. Pretreatment of the cells with deferoxamine also reduced their susceptibility to the cytotoxicity of Ox-LDL. The formation of thiobarbituric acid-reacting substances (TBARS) was observed in the cells exposed to Ox-LDL. Pretreatment of cells with deferoxamine reduced the formation of TBARS which was induced by Ox-LDL. These observations suggest that the toxicity of Ox-LDL to cultured endothelial cells involves the lipid peroxidation of cellular membrane catalyzed by iron derived from the target (endothelial) cells.