Neighborhood environments are increasingly recognized as a contextual determinant of health, behaviors, and disease; however, the pathways through which neighborhood characteristics impact health behaviors are poorly understood. This article examines pathways to elucidate how neighborhood social disorder may lead to HIV transmission. Data are from a baseline survey of 701 injection drug users from the Self-Help in Eliminating Lethal Diseases Study, an HIV prevention intervention in Baltimore. Structural equation modeling was used to examine the pathways among social disorder, psychological distress, and drug injection behaviors. The relationship between disorder and injection behaviors in the models tested suggests that psychological distress is higher in more socially disordered neighborhoods, that distress leads to greater injection frequency and equipment sharing, and that injection frequency predicts equipment sharing.