Comparative studies on regional HIV seroprevalence or seropositivity rate among injection drug users (IDUs) have focused primarily on assessing the risk factors for HIV infection. This study used a nonparametric analytic approach, known as standardization and decomposition, to to compare HIV seropositivity rates among IDUs between low- and high-HIV-prevalence regions in the United States. The regional difference in HIV seropositivity rate was decomposed into different components: (1) a "rate effect," which was attributed to the differences in factor-specific rates, and (2) "compositional factor effects," which were attributed to the differences in distributions of sociodemographic factors across regions. The analytic results show that the regional difference in HIV seropositivity rate was considerable (21.04%); however, the difference would be adjusted down to 17.65% if sociodemographic factors were proportionally distributed across the regions. Differential distribution of ethnic groups between the two regions accounted for about 15.02% of the regional difference in HIV seropositivity rate. The application of the standardization and decomposition method provides HIV researchers with opportunities to look at familiar data from a different perspective.