An explosive epidemic of human immunodeficiency virus type 1 (HIV-1) has been documented among injecting drug users (IDUs) in the former Soviet Union republics. In 1999, the two largest local IDU outbreaks of HIV-1 infection in the Russian Federation were registered in the Moscow and Irkutsk regions, where 13,004 HIV-1 cases were identified (44% of the total number of HIV-1 infections in Russia in 1999). To study the prevailing genetic variants and to estimate the genetic diversity of HIV-1 in these outbreaks, 60 samples from Moscow (n = 36) and from Irkutsk (n = 24) were analyzed using the gag/env heteroduplex mobility assay, and the env gp120 V3 encoding regions obtained from 23 individuals were sequenced. Both virus populations were highly homogeneous (the means of pairwise nucleotide distance were 1.75 +/- 0.83 and 2.35 +/- 1.59 for Irkutsk and Moscow, respectively), and similar to the subtype A viruses obtained earlier from IDUs in the former Soviet Union. The subtype A HIV-1 variant thus dominates in the largest HIV-1 outbreaks among IDUs in the Russian Federation.