As raloxifene is a mixed estrogen receptor agonist and antagonist, it exerts different effects on apoptosis in different tissues. In this study, we aimed to evaluate apoptosis in the peripheral lymphocytes of postmenopausal women treated with raloxifene and compare it with untreated control subjects. In this way, we expected to deduce some results about the effect of raloxifene on the immune system and to serve as a guide for future studies on this newly proposed effect of a well-known agent. Twenty osteoporotic postmenopausal women treated with raloxifene for 12 months were included in this study. Another 20 osteoporotic postmenopausal women matched for age and postmenopausal years, but without any medication, were chosen as the control group. Apoptosis was evaluated using a morphological and DNA fragmentation assay, in the peripheral lymphocytes of these women. Our results revealed a decrease in the apoptosis percentages of the patients treated with raloxifene (14.6%) with respect to the control subjects (15.8%), but the difference was not statistically significant (p = 0.467). This study indicated that raloxifene treatment had no apoptotic effect on peripheral human lymphocytes compared to controls. (c) 2006 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.