Persistently high rates of HIV infection in sub-Saharan Africa have driven the exploration for additional methods of prevention, such as microbicides. Multi-site, field-based clinical trials of microbicides are conducted in diverse social and cultural contexts. Local social and cultural perceptions of HIV/AIDS and sexual risk can have profound implications in shaping community responses to the clinical trials, thereby affecting enrollment and retention. Moreover, clinical trials may have a significant impact on trial participants with regard to their views of AIDS, health and relationships. Following these issues, this paper explores the subjective experiences of women enrolled in a microbicide feasibility study. Qualitative data were collected in two phases. The first phase took place prior to the inception of the feasibility study. Men and women from Soweto participated in focus group discussions about their perceptions and experiences of the AIDS epidemic and sexual risk. The second phase started once enrollment into the feasibility study had begun. Twenty-one women who were enrolled in the microbicide feasibility study were interviewed and participated in focus groups, and were asked about their experiences of participating in the microbicide feasibility study. Special attention was placed on how they felt their participation had affected their everyday lives. Interviews and discussions were conducted in local languages, recorded, translated and transcribed. Data were analysed thematically. The central finding of this study is the sense of empowerment that feasibility study participants felt in spite of their being embedded in a culture that has come to fear, deny or ignore AIDS. We discuss the critical role of repeated, voluntary counselling and testing, knowledge of HIV status, and heightened awareness of sexual and reproductive health in reshaping study participants' approaches to sexual relationships and AIDS, as well as the benefits that participation entailed.