The clinical core will provide access to both HlV positive and HIV negative women for study of the toxicity and effects of vaginal microbicides in humans. For preparation of raft cultures (project 2), vaginal and cervical biopsies will be obtained from healthy women without sexually transmitted diseases undergoing scheduled gynecological procedures requiring general regional anesthesia. Both HIV negative and HIV positive women will be studied twice weekly over the course of the menstrual cycle for determination of the changes in vaginal myeloperoxidase levels and flora over the cycle and the natural history of HlV detection in the genital tract among HIV positive women (project 3). Vaginal flora and myeloperoxidase levels will be compared between HIV positive and negative women in the same time of the menstrual cycle. Women will then be recruited to evaluate the effects of vaginal microbicides, both currently available agents (project 1) such as nonoxynol-9, chlorhexidine, and benzalkonium chloride, and H2O2- generating Lactobacillus, myeloperoxidase, and combination suppositories (project 3), and antimicrobial lipid mixtures (project 4) on the vaginal flora and epithelium. In addition, HIV positive women previously found to be HIV culture positive in the genital tract will be studied to evaluate the effects of vaginal microbicides on HIV detection in the genital tract. Only agents found to have acceptable toxicity profiles and reasonable antiviral and antibacterial activity in the organotypic culture system (project 2) and the primate model (project 1) will be tested on humans. Work done through this core will contribute to the overall project goals by confirming the safety and antimicrobial efficacy, including antiviral activity against HIV, of both currently available agents and microbicides developed as part of projects 3 and 4. The effects, both beneficial and detrimental, of microbicides on the complex microbiology and ecology of the vagina can only be studied definitively in humans.