BACKGROUND: The motivation for this paper is to inform the selection of future policy directions for tackling HIV/AIDS in Russia. The Russian Federation has more people living with HIV/AIDS than any other country in Europe, and nearly 70% of the known infections in Eastern Europe and Central Asia. The epidemic is particularly young, with 80% of those infected aged less than thirty, and no Russian region has escaped the detection of infections. However, measures to address the epidemic in Russia have been hampered by late recognition of the scale of the problem, poor data on HIV prevalence, potentially counterproductive narcotics legislation, and competing health priorities. An additional complication has been the relative lack of research into the spatial heterogeneity of the Russian HIV/AIDS epidemic, investigating the variety of prevalence rates in the constituent regions and questioning assumptions about the links between the epidemic and the circumstances of post-Soviet transformation. In the light of these recent developments, this paper presents research into the determinants of regional HIV prevalence levels in Russia. RESULTS: Statistical empirical research on HIV and other infectious diseases has identified a variety of factors that influence the spread and development of these diseases. In our empirical analysis of determinants of HIV prevalence in Russia at the regional level, we identify factors that are statistically related to the level of HIV prevalence in Russian regions, and obtain some indication of the relative importance of these factors. We estimate an empirical model that includes factors which describe economic and socio-cultural characteristics. CONCLUSION: Our analysis statistically identifies four main factors that influence HIV prevalence in Russian regions. Given the different nature of the factors that we identify to be of importance, we conclude that successful HIV intervention policies will need to be multidisciplinary in nature. Finally, we stress that further research is needed to obtain a better understanding of the statistical relations that we have identified; our empirical findings can serve as an important guide in these future research efforts, as they indicate which processes play an important role in regional HIV/AIDS prevalence rates in contemporary Russia.