The objective of this study was to examine the association between social isolation, domestic violence, and substance dependence among street-recruited female drug users. Hierarchical logistic regression was used to assess the independent contribution of social isolation and substance dependence to the likelihood that women will experience physical abuse. One hundred women (38.2%. N = 262) reported at least one incident of physical violence perpetrated by her most-recent sexual partner. Controlling for substance dependence and relationship status (the only significantly associated demographic variable), women reporting indicators of social isolation were more likely to have been physically abused by their most-recent sexual partners than nonisolated women. Substance dependence was not related significantly to domestic violence. Providers who have contact with female drug users should be aware of the high domestic violence rates and work to counterbalance the isolation these women may experience.