INTRODUCTION: The HIV/AIDS epidemic in St Petersburg, as in much of Russia, is concentrated among injection drug users (IDU) in whom prevalence reached 30% in 2003. Understanding the dynamics of the epidemic is important in developing appropriate responses in the resource-constrained context of Russian cities such as St Petersburg. METHODS: IDU were contacted and screened to create a seronegative cohort for prevention and vaccine studies. At screening, individuals provided sociodemographic, drug use, and injection and sex-related risk behavior data. Seronegative individuals who enrolled in the cohort were followed for one year and tested for HIV semiannually. Residential addresses were entered into a geographical information system programme and analysed for spatial clustering using Moran's I and nearest-neighbor analysis. RESULTS: We mapped 788 of the 900 study participants to discrete locations within St Petersburg; 236 (29.9%) were HIV seropositive at baseline. Although there was no clustering of the study population as a whole, HIV-infected individuals were tightly clustered and prevalence co-clustered with high frequency of heroin injection, receptive syringe sharing, being younger than 24 years, and living with parents. These clusters were restricted to 5% of populated areas of the city. We mapped 18 of 20 incident cases detected among the cohort, and more than half were located within or adjacent to the clusters. INTERPRETATION: Spatial analysis identified linkages between disease prevalence and risky injection behaviors that were not evident using traditional epidemiological analysis. The analysis also identified where resources might be allocated geographically for maximum impact in slowing the HIV epidemic among IDU.