In order to study estrogen absorption from the vagina, 0.5 mg of unconjugated estrone (E1) or 17beta-estradiol (E2) was administered vaginally to 10 postmenopausal patients. A 29-fold increase in plasma E2 and a 4-fold increase in plasma E1 concentrations were observed 1 hour following the vaginal deposition of 0.5 mg of E2. Maximal decreases of 25% and 37% in plasma levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), respectively, were observed at 5 hours following treatment. One hour after vaginal administration of 0.5 mg of E1, a 24-fold increase in plasma E1 and a 3.7-fold increase in E2 were observed. These increases were associated with a 30% decrease in plasma FSH and LH. These data indicate that the vaginal administration of E2 or E1 may be used to achieve physiologic blood levels of these estrogens. They further suggest that vaginal estrogens not be used in patients in whom systemic estrogen therapy is contraindicated.