LONGITUDINAL RESEARCH ON street-recruited out-of-treatment drug users involves ethical issues concerning enrollment and retention of participants, remuneration and benefits. In contrast to practices of excluding such high-risk populations from research and assuming that they would not comply with a protocol requiring repeated measures over a 12-month period, this report presents examples from 15 years of community-based studies that have enrolled drug-using participants and achieved a 96% retention rate. We also examine ethical issues connected with cash remuneration, and describe methods to elucidate the kinds of benefits that are most meaningful to this population. Findings suggest that the research community must reconsider the ethics of blanket exclusions of such high-risk subjects, and make evidence-based decisions about recruitment, retention, remuneration, and benefits.