Estrogen receptor content in vaginal tissue was quantified in 12 healthy female volunteers during the menstrual cycle. Epithelial biopsies were obtained at cycle days 10 and 21 and investigated by a monoclonal enzyme immunoassay. Measurable amounts of estrogen receptors were found in all women at both sampling occasions. In women with an ovulatory menstrual cycle, a significant fall inVreceptor content was recorded during the luteal phase. Structural and functional changes in the vaginal epithelium during the menstrual cycle may be important for the diagnosis and susceptibility to certain viral infections.