To determine the anticipated participation in a prophylactic AIDS vaccine trial and to identify perceived benefits and barriers to enrollment of HIV-seronegative volunteers at risk of HIV infection in northern Thailand. A cross-sectional survey. Subjects interviewed in a cross-sectional survey included female commercial sex workers (n = 215), men attending sexually transmitted disease clinics (n = 219), conscripts in the Royal Thai Army (n = 1453), and men discharged from the army (n = 293) who had returned to civilian life. We determined AIDS vaccine knowledge and attitudes, perceived vulnerability to HIV infection, barriers and incentives to participate in a future vaccine trial and agreement to participate in a randomized trial. Awareness of vaccines (88-97%) and AIDS vaccine development efforts (62-77%) were common and viewed to be a complement to behavior change (74-94%). Approximately 25% of subjects would definitely join a trial if asked, and an additional 38% would accept an AIDS vaccine if they were convinced it would be safe and effective. Important barriers to participation included concerns with discrimination (16-45%), short- (37-60%) and long-term (30-55%) vaccine side-effects, fear of disability and death (36-58%), and beliefs that partners would refuse to have sex (24-49%) after immunization. The principal inducement to join a trial was health insurance (62%). Potential HIV vaccine trial participants have several fears of joining a vaccine study at this time. Information derived from Phase I/II trials is needed to address these concerns if enrollment in efficacy trials is to be successful in the near future.