The complex relationship between sex hormones and immune function suggests that sex hormone deficiency and estrogen replacement therapy (ERT) in post-menopausal women may have pleiotropic effects on immune function. For this reason, we aimed to investigate short-term effects of surgical menopause and ERT on immunity profile in peri-menopausal women. Seventeen healthy peri-menopausal women who were to undergo total abdominal hysterectomy and bilateral salpingo-oopherectomy (TAH + BSO) for uterine myoma were enrolled into this study. Three blood samples were collected from each patient: 1-day prior to surgery, 30 days after the operation (before ERT) and 30 days after transdermal ERT. The percentages of peripheral blood lymphocyte subpopulations, serum interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) concentrations were determined by flow-cytometry and ELISA, respectively. Following TAH + BSO, the percentage of CD8+ cells was increased ( P < 0.001 ) while the percentage of CD19+ cells, serum IL-4, and IFN-gamma concentration and the ratio of CD4+ to CD8+ cells were decreased ( P < 0.001, P < 0.001, P < 0.002, and P < 0.05 respectively). After ERT, this trend reversed and a decrease in the CD8+ cells ( P < 0.001 ), increase in the CD19+ cells percentages ( P < 0.02 ) and increase in serum IFN-gamma concentration ( P < 0.002 ) were observed. Although an increasing trend in the CD4+ to CD8+ ratio occurred by ERT, this was not significant. However, the decrease in the serum IL-4 concentration after TAH + BSO was not reversed by ERT. Hormone deficiency in post-menopausal women may cause an impaired immune response, and ERT can restore this phenomenon. Estrogen seems to have an important role in the regulation of immune function.