To gauge interest about participation in human immunodeficiency virus type 1 (HIV vaccines, we interviewed 375 HIV-seronegative injecting drug users who are participants in an ongoing longitudinal study of HIV infection. Nearly all (93%) responded that they thought it likely that an HIV vaccine would become available, and 85% expressed interest in participating in a study of vaccine effectiveness. However, levels of interest decreased to 47% when respondents were informed that the vaccine might result in a positive HIV test and to 27% when offered to be in a study where the vaccine might contain a piece of the virus. Factors that increased interest in trial participation included assurances of confidentiality, being fully informed about the protocol and remuneration. Most respondents (78%) felt that injecting drug users would maintain other risk reduction activities (e.g., condom use) if they participated in a vaccine study. These data suggest a high level of interest for participation in HIV vaccine trials, but that more education about vaccines and the risks involved is needed. Ongoing communication with the community and responsiveness to community concerns is crucial to achieve a successful vaccine study.