The effects of hormone replacement therapy (HRT) on lymphocytes and granulocytes have never been determined in detail. Ten healthy menopausal women (age 49-51 years; menopause less than 2 years) were treated for 6 months by administering transdermal estradiol (100 micrograms/day for 21 consecutive days) and oral medroxyprogesterone acetate (10 mg/day from day 10 to day 21). Days 22-28 were therapy-free. All subjects were examined during the first and the last month of treatment: evaluations were carried out on days 0, 8, 21 and 28. CD4+CD45RO+ cells were found to be significantly reduced on day 8. CD56+ cells and CD8+CD11b+ cells were decreased on day 21 and recovered basal level on day 28. Natural killer cell function was transiently increased on day 8 and greatly reduced on day 21. During the first month of therapy, the expression of Leu8 and CD11b antigens on granulocyte membranes was significantly affected by HRT. Taken together, the results indicate that HRT selectively affects various immune cell subsets.