We conducted Community-Based Participatory Research (CBPR), using a qualitative focus group design, to assess factors that might impact participation of high-risk impoverished adults in future HIV Vaccine Trials (HIVVTs). The participants were 40 homeless and low-income adults recruited from subsidized apartments and homeless shelters in Los Angeles. Findings revealed that the participants expressed both concerns and interest in future HIVVTs. Concerns centered on the impact of the vaccine on their physical health, the possibility of seroconverting and its associated stigma. While distrust of the government was pervasive, the participants were interested in receiving more information about the vaccine from the researchers. They also wished to have their voices heard by the researchers early in the design of the vaccines. Motivating factors were also discovered, and included altruism, compensation and access to care. Perception that risk behaviors might increase among some as a result of participation in a future HIVVT was likewise revealed. Implications of the study reveal that while impoverished populations are interested in participating in future HIVVTs, the researchers must address concerns early on. Moreover, the importance of ongoing education and counseling to warn about hazards of engaging in risky behavior while participating in a future HIVVT was critical.