Oxidative stress is suggested to play an important role in the pathogenesis of cardiovascular disease (CVD). Various hormone replacement therapy (HRT) protocols are used to reduce the CVD risk in postmenopausal women. Recent studies found that HRT lowers lipid levels and improves vascular endothelial function in postmenopausal women. In this study the effects of HRT on plasma and platelet membrane fatty acid composition and the oxidant-antioxidant system in postmenopausal women are investigated. Blood samples were obtained from 50 postmenopausal women. Before starting treatment, all participants underwent clinical, biochemical and hormonal screening procedures including gynecologic and physical breast examination. Then oral HRT (2mg estrodiol valerate+1mg cyproterone acetate) were given to all subjects for 1 year. Levels of malondialdehyde (MDA), total thiol (t-SH) and fatty acid contents, activities of glutathione-Stransferase (GST) and superoxide dismutase (SOD) were measured before and after treatment. Platelet membrane palmitic, stearic and oleic acid contents decreased (6.5%, 22.5% and 21.9% respectively) and linoleic and arachidonic acid contents increased (21.2% and 25.4% respectively) after HRT. Platelet MDA, GST and SOD levels were lower and t-SH content was higher than pre-treatment levels. These results indicate that hormone replacement therapy may affect platelet membrane fatty acid content and oxidant-antioxidant balance in postmenopausal women.