The purpose of this study was to explore the associations among living arrangements, HIV seroprevalence, and HIV risk and protective factors among 1,322 drug users participating in the University of Miami CARES (Community AIDS Research and Evaluation Studies) HIV intervention program. Living arrangements may be associated with HIV prevention behaviors; however, these influences can be either protective or destructive and therefore merit further examination. Statistical analyses indicated differences in the living arrangements of women compared with men, and significant associations were noted among women's living arrangements, HIV seroprevalence, risk behaviors and protective behaviors. The data from this study suggest that future HIV prevention research should investigate not only high-risk individuals, but persons with whom they interact often, especially those with whom they live or with whom they have sex. The next phase of HIV and drug interventions should be attentive to the incorporation of social context and social influences, paying particular attention to understudied populations such as high-risk women.