Syringe exchange programs (SEPs) aim to reduce the harm associated with injection drug use (IDU). Although they have been accepted as critical components of HIV prevention in many parts of the world, they are often unwelcome and difficult to set up and maintain, even in communities hardest hit by IDU-related HIV transmission. This research examines socio-cultural and political processes that shape community and institutional resistance toward establishing and maintaining SEPs. These processes are configured and reinforced through the socio-spatial stigmatizing of IDUs, and legal and public policy against SEPs. Overarching themes the paper considers are: (1) institutional and/or political opposition based on (a) political and law enforcement issues associated with state drug paraphernalia laws and local syringe laws; (b) harassment of drug users and resistance to services for drug users by local politicians and police; and (c) state and local government (in)action or opposition; and (2) the stigmatization of drug users and location of SEPs in local neighborhoods and business districts. Rather than be explained by "not in my back yard" localism, this pattern seems best conceptualized as an "inequitable exclusion alliance" (IEA) that institutionalizes national and local stigmatizing of drug users and other vulnerable populations.