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We investigated the oxidative state of low-density lipoprotein (LDL) in patients with beta-thalassemia to determine whether there was an association with atherogenesis. Conjugated diene lipid hydroperoxides (CD) and the level of major lipid antioxidants in LDL, as well as modified LDL protein, were evaluated in 35 beta-thalassemia intermedia patients, aged 10 to 60, and compared with age-matched healthy controls. Vitamin E and beta-carotene levels in LDL from patients were 45% and 24% of that observed in healthy controls, respectively. In contrast, the mean amount of LDL-CD was threefold higher and lysil residues of apo B-100 were decreased by 17%. LDL-CD in thalassemia patients showed a strong inverse correlation with LDL vitamin E (r = -0.784; P <.0001), while a negative trend was observed with LDL-beta-carotene (r = -0.443; P =.149). In the plasma of thalassemia patients, malondialdehyde (MDA), a byproduct of lipid peroxidation, was increased by about twofold, while vitamin E showed a 52% decrease versus healthy controls. LDL-CD were inversely correlated with plasma vitamin E (r = -0.659; P <.0001) and correlated positively with plasma MDA (r = 0.621; P <. 0001). Plasma ferritin was positively correlated with LDL-CD (r = 0.583; P =.0002). No correlation was found between the age of the patients and plasma MDA or LDL-CD. The LDL from thalassemia patients was cytotoxic to cultured human fibroblasts and cytotoxicity increased with the content of lipid peroxidation products. Clinical evidence of mild to severe vascular complications in nine of the patients was then matched with levels of LDL-CD, which were 36% to 118% higher than the mean levels of the patients. Our results could account for the incidence of atherogenic vascular diseases often reported in beta-thalassemia patients. We suggest that the level of plasma MDA in beta-thalassemia patients may represent a sensitive index of the oxidative status of LDL in vivo and of its potential atherogenicity.