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In South Africa, information on HIV among men who have sex with men (MSM) is limited, and HIV prevention programs for men MSM are not widely available, despite global evidence that MSM are at substantial risk for HIV infection. The Johannesburg/eThekwini Men's Study was conducted during 2008 to provide information on HIV among MSM in Johannesburg and Durban.MSM aged 18 years or older were recruited using respondent-driven sampling. Participants completed a questionnaire and provided finger-prick blood specimens for anonymous HIV testing in a laboratory.From July to December 2008, 285 MSM were recruited in Johannesburg (n = 204) and Durban (n = 81). Participants had a median age of 22 years and were predominantly black Africans (88.3%). The HIV prevalence was 49.5% [95% confidence interval (CI): 42.5% to 56.5%] in Johannesburg and 27.5% [95% CI: 17.0% to 38.1%] in Durban. HIV infection was associated with gay identification [adjusted odds ratio (aOR): 8.4; 95% CI: 3.7 to 19]. Factors in the previous year that were associated with HIV infection included receptive unprotected anal intercourse [aOR 4.3; 95% CI: 2.4 to 7.6]; sex with a person known to be HIV positive [aOR: 2.3; 95% CI: 1.1 to 4.9]; and a sexually transmitted infection diagnosis [aOR 2.4; 95% CI: 1.1 to 5.2].HIV prevalence among MSM in Johannesburg and Durban is considerably higher compared with men in the general population. There is an urgent need to establish national HIV surveillance among MSM and to expand the availability of HIV prevention programs for MSM. [ABSTRACT FROM AUTHOR]