Under-representation of minority populations, particularly African Americans, in HIV/AIDS research is problematic because African Americans bear a greater disease burden from HIV/AIDS. Studies of motivations for participating in research have emphasized factors affecting individuals' willingness to participate and barriers to participation, especially in regard to HIV vaccine research. Little is known about how underserved minority drug users perceive research and their decisions to participate. This study describes African American drug users' perceptions of research participation and their decisions to participate based on three kinds of hypothetical HIV/AIDS-related clinical studies. In-depth, qualitative interviews were conducted with 37 underserved, African American crack cocaine users, recruited from participants already enrolled in three different behavioral HIV prevention studies. Interviews were recorded, transcribed, coded for themes and sub-themes and analyzed using directed and conventional content analysis. Participants' decisions to take part in research often involved multiple motivations for participating. In addition, decisions to participate were characterized by four themes: a desire for information; skepticism and mistrust of research and researchers; perceptions of medical care and monitoring within a study; and participant control in decisions to participate or decline participation. Lack of adequate information and/or medical care and monitoring within a study were related to mistrust, while the provision of information was viewed by some individuals as a right and acknowledgement of the participant's contribution to the study. Participants perceived, rightly or wrongly, that medical monitoring would control some of the risks of a study. Participants also described situations of exerting control over decisions to enter or withdraw from a research study. Preliminary findings suggest that continuous communication and provision of information may enhance enrollment and adherence. Further exploration of decisions to participate in research will add to the understanding of this complex phenomenon and enhance the ability of individuals with HIV/AIDS to benefit from research.