The increase in incidence of oral discomfort among women in a menopause is probably due to hormone modifications. This study evaluated the efficacy of hormone replacement therapy in 27 postmenopausal patients, aged 48 to 58 years, with oral discomfort and no local irritants and in 47 postmenopausal women with no oral discomfort. Patients were treated with conjugated estrogens for 21 days and medroxyprogesterone acetate from day 12 through day 21. Hormone-replacement therapy had no effect on oral cytology in the 40 symptom-free postmenopausal women compared with a group of 47 postmenopausal women who had no oral symptoms and were not treated. Hormone-replacement therapy relieved symptoms and improved oral cytohormonal features in 15 of 27 patients with symptoms. Nuclear estrogen receptors were found by immunohistochemical assay in 8 of 10 randomly selected patients with symptoms who responded to hormone-replacement therapy, but not in 2 patients who did not benefit from hormone-replacement therapy. Estrogen receptors were also found in 6 of 10 fertile women with no oral disease. Our results suggest that oral discomfort may be related to steroid hormone withdrawal only in some postmenopausal women and that replacement therapy may improve the clinical picture and cytologic features in this group of patients. Immunohistochemical identification of estrogen receptors may help to identify patients for whom hormone-replacement therapy may be beneficial.