The vagina is the staging site for many genital infections. The long-term goal of this project is to understand how use of vaginal products could increase or decrease susceptibility to infections acquired during sexual intercourse. Vaginal resistance to the development of infection is largely dependent upon three components: normal vaginal flora which inhibits microorganisms by producing a low pH and hydrogen peroxide, reducing the attachment of bacteria to the vaginal epithelium which reduces the ability of the bacteria to establish colonization, and an intact vaginal epithelium which mechanically resists invasion. Many prescribed and over- the-counter products placed in the vagina are known to potentially effect one or more of these vaginal protective mechanisms. This proposal is designed to examine the effects of a variety of conditions and products on the vaginal physiology. The effects under study include vaginal discharge, vaginal microbial flora, attachment of bacteria to vaginal epithelium and the cytology and histology of the vaginal epithelium. Quantitative vaginal cultures will be performed for selected species, attachment of Lactobacillus and Escherichia coli to the subject's vaginal epithelial cells will be examined and colposcopic, cytologic and histologic examination of the vaginal cell epithelium will be studied at baseline and under experimental conditions. We intend to examine the following conditions for their effect on the vaginal physiology: the normal menstrual cycle in the proliferative, luteal and menstrual phase, hormonal contraception, sexual intercourse with and without condoms, a variety of doses and frequent use of intravaginal spermicide containing nonoxynol-9, commonly used vaginal douche products, including one that contains povidone-iodine, the intravaginal instillation of hydrogen peroxide producing Lactobacillus, and menopause before and after estrogen replacement therapy. The research is intended to answer some of the questions of whether bacterial attachment varies during the menstrual cycle, under which conditions bacteria introduced into the vagina during intercourse contributes to the overgrowth of lactobacilli, the effect of hormonal contraception on bacterial growth, bacterial cell attachment and the epithelium, whether nonoxynol-9 or povidone-iodine use disturbs bacterial flora and causes vaginal epithelial damage, and if so, the extent of the damage, conditions where intravaginal Lactobacillus instillation leads to vaginal colonization and the effect of menopause and estrogen replacement on vaginal flora and bacterial attachment. Use of female-controlled vaginal microbicides will be an important public health measure to decrease the heterosexual transmission of sexually transmitted diseases including human immunodeficiency virus. The proposed studies will provide critical new information on endogenous and exogenous factors which effect vaginal physiology, and thereby alter resistance of the vagina to infection.