To determine the prevalence of HIV infection, HIV risk factors, and exposure to national HIV prevention programs, and to identify factors associated with HIV infection among South African youth, aged 15-24 years. A cross-sectional, nationally representative, household survey. From March to August 2003 we conducted a national survey of HIV prevalence and sexual behavior among 11 904 15-24 year olds. Multivariable models for HIV infection were restricted to sexually experienced youth. Young women were significantly more likely to be infected with HIV in comparison with young men (15.5 versus 4.8%). Among men, a history of genital ulcers in the past 12 months was associated with HIV infection [adjusted odds ratio (AOR), 1.91; 95% confidence interval (CI), 1.04-3.49) whereas among women a history of unusual vaginal discharge in the past 12 months was associated with HIV infection (AOR, 1.75; 95% CI, 1.26-2.44). Young women with older partners were also at increased risk of HIV infection. Among both men and women, increasing partner numbers and inconsistent condom use were significantly associated with HIV infection. Males and females who reported participation in at least one loveLife program were less likely to be infected with HIV (AOR, 0.60; 95% CI, 0.40-0.89; AOR, 0.61; 95% CI, 0.43-0.85, respectively). This survey confirms the high HIV prevalence among young people in South Africa and, in particular, young women's disproportionate risk. Programs for youth must continue to promote partner reduction, consistent condom use and prompt treatment for sexually transmitted infections while also addressing contextual factors that make it difficult for them to implement behavior change.