Residential transience may contribute to adverse mental health. However, to date, this relationship has not been well-investigated among urban, impoverished populations. In a sample of drug users and their social network members (n=1,024), we assessed the relationship between transience (frequently moving in the past 6 months) and depressive symptoms, measured by the CES-D, among men and women. Even after adjusting for homelessness, high levels of depressive symptoms were 2.29 [95%CI= 1.29-4.07] times more likely among transient men compared to nontransient men and 3.30 [95% CI=1.10-9.90] times more common among transient women compared to nontransient women. Stable housing and mental health services need to be available, easily accessible, and designed so that they remain amenable to utilization under transient circumstances.