Objective: To investigate the relationship between raloxifene administration and serum malondialdehyde (MDA), erythrocyte superoxide dismutase (SOD), erythrocyte glutathione peroxidase (GPx) levels in healthy postmenopausal women. Methods: In a randomized and placebo-controlled design, 80 women received either 60 mg/day raloxifene or placebo for 24 weeks. MDA, SOD, and GPx levels were assessed at 0,4,12, and 24 weeks. Wilcoxon signed-rank test and Mann-Whitney U test were used for comparisons. Results: Six women in the treatment arm and eight women in the placebo group discontinued the study. Mean serum MDA levels were significantly (p = 0.001) decreased from 11.4 nmol/ml at baseline to 8.9 nmol/ml at week 12 with raloxifene treatment. Mean erythrocyte SOD activity was significantly (p = 0.02) reduced from 1472 U/g Hb at baseline to 1173 U/g Hb at week 12 following raloxifene administration. Lowered serum MDA and erythrocyte SOD levels persisted during treatment. On contrary, erythrocyte GPx levels did not change significantly with raloxifene administration. Conclusions: Raloxifene (60 mg/day) lowers serum MDA levels and erythrocyte SOD activity in postmenopausal women after 12 weeks of treatment. The clinical implications of these findings need to be determined. (c) 2004 Elsevier Ireland Ltd. All rights reserved.