The aim of this paper is to study how structural determinants and the role of injecting drug users (IDUs) as a bridging population to the general population affected the AIDS subepidemic in southern Brazil during 1986–2000. Data from 288 southernmost Brazilian municipalities were analyzed. Using hierarchical modeling and inputs from a Geographic Information System, a multilevel model was constructed. The dependent variable was the logged AIDS standardized incidence rate (among the heterosexual population aged 15–69-years-old); independent variables included indicators for education, water provision, sewage, and garbage collection, per capita income, Gini coefficient (on income), Human Development Index, indicators of accessibility, and AIDS rate among IDUs. Significant predictors included AIDS rate among IDUs, distance from/to highways/railways, the Human Development Index and the ratio of residents who have access to sanitary installations. Poverty (as measured by socioeconomic indicators) and bridging from IDUs contribute to the spread of HIV/AIDS in Brazilian southern municipalities