To better understand the prevalence, incidence, and risk factors for sexually transmitted diseases (STDs) among female adolescents, a prospective 6-month cohort study was conducted at four teen clinics in a southeastern city. At enrollment, 260 (40%) of 650 sexually active females ages 14-19 years had an STD: chlamydia, 27%; herpes simplex virus type 2 (HSV-2), 14%; gonorrhea, 6%; trichomoniasis, 3%; and hepatitis B, 2%. At follow-up, 112 (23%) of 501 participants had an incident infection: chlamydia, 18%; HSV-2, 4%; gonorrhea, 4%; and trichomoniasis, 3%. At either enrollment or follow-up, 53% had >/=1 STD; of those with 1 lifetime partner, 30% had an STD. Having a new partner (odds ratio [OR], 2.2; 95% confidence interval [CI], 1. 1-4.2) or friends who sell cocaine (OR, 1.6; CI, 1.0-2.6) was independently associated with incident infection. STD incidence and prevalence were extremely high in this population, even in teenagers with only 1 lifetime partner. Individual risk behaviors appeared less important for STD risk than population factors.