PURPOSE: Vaginal microbicides will provide a woman-initiated prevention strategy that could substantially reduce rates of HIV infection. The acceptability of microbicides will greatly influence the use and, hence, effectiveness of such products. In this study, the acceptability of an investigational microbicide, PRO 2000 Gel (Indevus Pharmaceuticals, Inc., Lexington, MA), was assessed, and women's opinions about microbicides and their potential for real world use were gathered. METHODS: Quantitative and qualitative data were collected from 30 U.S. and 33 South African women. All sexually active HIV-uninfected women and all sexually abstinent HIV-infected women participating in this phase I clinical trial stated in a survey that they would use PRO 2000 Gel if they had reason to be concerned about HIV and the product were available. Qualitative data, however, provided insight into the nuances of acceptability ratings. Women rated product safety, ease of use, and positive effects on sexual pleasure among the most important characteristics of acceptable microbicides. RESULTS: Opinions regarding product leakage, contraceptive capability, and the ability to be used without partners noticing, as well as characteristics of the product itself, varied substantially based on the context of sex and perceptions of risk within each individual woman's life. CONCLUSIONS: As microbicide development continues and the first investigational products move into efficacy trials, the needs and preferences of those women who constitute the potential users of microbicides become paramount. Providing woman-initiated microbicides that are safe, easy to use, and pleasurable will be key to the impact these products will have on the AIDS epidemic worldwide.