The objective of this study was to estimate the global distribution and regional spread of different HIV-1 genetic subtypes and circulating recombinant forms (CRFs) in the year 2000. These estimates were made based on data derived from global HIV/AIDS surveillance and molecular virology studies. HIV-1 incidence during the year 2000 was estimated in defined geographic regions, using a country-specific model developed by WHO-UNAIDS. The proportion of new infections caused by different HIV-1 subtypes in the same geographic regions was estimated by experts from the WHO-UNAIDS Network for HIV Isolation and Characterization, based on results generated by HIV molecular epidemiology studies in 1998 to 2000. The absolute numbers and relative proportions of new infections due to different genetic subtypes of HIV-1 by different geographic regions were calculated using these two sets of estimated data. The results of the study demonstrated that the epidemiology of HIV-1 subtypes and CRFs is characterized by their differential distribution and varying significance as a driving cause of the pandemic on regional and global basis. The largest proportion of HIV-1 infections in the year 2000 was due to subtype C strains (47.2%). Subtype A/+CRF02_AG was estimated to be the second leading cause of the pandemic (27%), followed by subtype B strains (12.3%). The same analysis confirmed an increasing role of HIV-1 CRFs in the pandemic. The authors conclude that combined analysis of data based on the global HIV/AIDS surveillance and molecular virology studies provides for a useful model to monitor the dynamics of the global spread of HIV-1 subtypes and CRFs on regional and country levels-the information of potential importance for diagnosis and treatment of HIV/AIDS, as well as for the development globally effective HIV vaccines.