Lipid peroxidation is a central feature of oxidant injury that leads to the vascular disease associated with systemic lupus erythematosus (SLE). In the past, lipid peroxidation has been difficult to measure. Because isoprostanes are thought to have particular relevance in vascular disease, we set out to measure, in vivo, serum concentrations of 8-isoprostaglandin F2 alpha (8-iso-PGF2alpha) as a marker of oxidative stress to evaluate the occurrence and ascertain the significance of lipid peroxidation in SLE.Sixty patients with SLE and 20 age- and sex-matched controls were recruited. Patients were assessed according to a standard protocol, including demographic, clinical, laboratory and treatment variables. We measured the serum concentrations of 8-iso-PGF2alpha using the enzyme-linked immunoabsorbent assay. Fasting lipid profiles and serum lipid peroxide concentrations were also assessed in both SLE patients and controls.In SLE patients, with a mean age of 22.4 (standard deviation [SD] 2.7) years and a disease duration of 20.9 (SD 4.9) months, the serum concentrations of 8-iso-PGF2alpha were higher than in the age- and sex-matched controls (p < 0.001). The mean level of 8-iso-PGF2alpha in SLE patients was 466 (SD 296.8) pg/mL compared with a mean of 90.9 (SD 26.6) pg/mL in the control group (p < 0.001). Our findings revealed a dose-response relationship between 8-iso-PGF2alpha concentrations and the dosage of prednisone. The level of serum lipid peroxide in SLE patients was increased compared with levels measured in the control group.Our findings suggest that oxidative stress is implicated in the pathogenesis of SLE and that 8-iso-PGF2alpha can be used as a sensitive, noninvasive, reliable marker of oxidative stress in vivo. Furthermore, it should be possible to target therapies more effectively so that the detrimental actions of vascular oxygen free radicals can be reduced.