Information is sparse on the social context of illicit drug injection behaviors and their relationship to HIV infection. This study examined relationships between injection settings, injecting with others, and HIV risk behaviors of sharing needles and not cleaning contaminated needles in a sample of 630 inner-city injecting drug users in Baltimore, MD. Through open-ended interviews, five primary settings of injection behavior were identified. These settings included one's own, friends' and mother's residence, shooting galleries, and semipublic areas. Most participants reported injecting in their own residence (92%) and friends' residence (86%) in the prior 6 months. In a multiple regression analysis, injecting at friends' residence, in shooting galleries, and in semipublic areas and frequency of injecting with others were significantly associated with frequency of sharing uncleaned needles, “slipping” (i.e., failure to disinfect shared needles), and not always cleaning used needles before injecting. Results suggest that interventions may benefit from targeting settings as well as behaviors to reduce the spread of HIV.