The relationships between commercial sex work, drug use, and sexually transmitted infections (STI) in St. Petersburg, Russia were assessed using qualitative research methods and an examination of existing research, surveillance and epidemiology data. The rapid assessment methodology included in-depth qualitative interviews with key informants, naturalistic observations of commercial sex work and drug use sites, geo-mapping, and a critical review of the available surveillance, epidemiology, and sociological data. Patterns of commercial sex work and drug use in St. Petersburg are described. The existing surveillance data attributes infections to injected drug use over and above any other risk category. However, examination of the clinic and epidemiology data suggests that HIV infection may be increasing fastest among groups that are acquiring HIV through sexual transmission. Targeted screening studies of STI and HIV morbidity among populations that are not included in the surveillance algorithm are needed, such as commercial sex workers, street youth, and the homeless. Sexual history taking to better characterize the proportion of cases that result from sex between male partners would also be helpful.