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To estimate age- and sex-specific herpes simplex virus type-2 (HSV-2) prevalence in urban African adult populations and to identify factors associated with infection.Cross-sectional, population-based samples of about 2000 adults interviewed in each of the following cities: Cotonou, Benin; Yaoundé, Cameroon; Kisumu, Kenya and Ndola, Zambia. Consenting study participants were tested for HIV, HSV-2 and other sexually transmitted infections.HSV-2 prevalence was over 50% among women and over 25% among men in Yaoundé, Kisumu and Ndola, with notably high rates of infection among young women in Kisumu and Ndola (39% and 23%, respectively, among women aged 15-19 years). The prevalence in Cotonou was lower (30% in women and 12% in men). Multivariate analysis showed that HSV-2 prevalence was significantly associated with older age, ever being married, and number of lifetime sexual partners, in almost all cities and both sexes. There was also a strong, consistent association with HIV infection. Among women, the adjusted odds ratios for the association between HSV-2 and HIV infections ranged from 4.0 [95% confidence interval (CI) = 2.0-8.0] in Kisumu to 5.5 (95% CI = 1.7-18) in Yaoundé, and those among men ranged from 4.6 (95% CI = 2.7-7.7) in Ndola to 7.9 (95% CI = 4.1-15) in Kisumu.HSV-2 infection is highly prevalent in these populations, even at young ages, and is strongly associated with HIV at an individual level. At a population level, HSV-2 prevalence was highest in Kisumu and Ndola, the cities with the highest HIV rates, although rates were also high among women in Yaoundé, where there are high rates of partner change but relatively little HIV infection. The high prevalence of both infections among young people underlines the need for education and counselling among adolescents.