OBJECTIVE: To estimate the prevalence of HIV and Chlamydia trachomatis (CT) infections amongst adolescents in rural Mwanza Region, Tanzania and their association with demographic variables. DESIGN: Population-based cross-sectional survey. METHODS: All 15--19-year olds living in households selected by random cluster sampling were invited to participate. After interview, urine was tested for HIV and CT. RESULTS: 9445 15--19-year olds were enrolled. HIV prevalence was 0.6% (95% CI: 0.4--0.8%) in males and 2.4% (95% CI: 2.0--2.8%) in females, and increased steeply with age (trend: P < 0.006 and P < 0.001, respectively). After adjustment for age, risk of HIV infection was significantly associated with female sex (OR=4.3), never having been to primary school in males (OR=2.7), and current symptoms of genital discharge (OR=2.3) or genital ulcer (OR=5.3) in females. The prevalence of CT was 1.0% (95% CI: 0.8--1.4%) in males and 2.4% (95% CI: 2.0-2.9%) in females. After adjustment for age, CT infection was associated with female sex (OR=2.4), reported current symptoms of STD (males OR=2.5, females OR=1.9) and positive leucocyte esterase (LE) test (males OR=3.1, females OR=2.6). Eighty-two percent of males and 79% of females with CT were asymptomatic. There was no association between CT and HIV infection in either sex. CONCLUSIONS: There is a high prevalence of HIV and CT amongst adolescents, especially young women, in this rural population, highlighting the need for effective interventions to improve adolescent reproductive health. The high rates of asymptomatic infection imply that innovative strategies are needed to reach and treat young people with STD.