We present the findings of a qualitative investigation into the factors that may enable or inhibit participation in a future HIV vaccine trial. Thirty-seven semi-structured interviews and two focus groups were conducted with trial site community members who had attended HIV vaccine education workshops conducted by the community involvement programme of the South African AIDS Vaccine Initiative (SAAVI). Our findings indicate that enablers and inhibitors to participation in HIV vaccine trials may. be further classified as either abstract or concrete. Each sub-theme was classified as an abstract inhibitor, abstract enabler, concrete inhibitor, or concrete enabler. Abstract inhibitors were fear of illness or death, lack of information about HIV/AIDS and HIV vaccines, and an HIV vaccine trial's association with HIV/AIDS. Abstract enablers were participants' reported sense of altruism and quality of life issues, such as protection from becoming infected with HIV. Concrete inhibitors were the monetary costs associated with participation, fear of being tested for HIV and receiving test results, negative reactions from family and community members, time delays between receiving trial participation information and actual enrolment, and a general mistrust of researchers. Concrete enablers were practicalities and convenience, financial rewards, a safe testing environment, positive family reactions to trial participation, the different levels of participation available to different members of the community, the salience of HIV in communities, positive community reactions to vaccine trials, and the presence of role models. In addition to these quadrants, the enablers and inhibitors have also been located within a contextual framework that includes the individual; family, community, and societal levels. Our research contributes to an understanding of the concerns of potential HIV vaccine trial participants within the South African context. Our findings illustrate the applicability of international research to proposed vaccine-trial activities in South Africa and should, therefore, inform the development and implementation of successful community preparedness activities.