Background: Studies assessing the validity attributed to self-reported measures of sexually transmitted diseases (STDs) clearly are needed, particularly those used for high-risk populations such as female adolescents, in whom STD prevention is a priority. Goal: To determine the accuracy of self-reported STD test results in female adolescents over a relatively brief period (≈28 days). Study Design: A prospective, randomized, controlled clinical trial of STD/HIV prevention for African American females, ages 14 to 18, was conducted. Study participants were recruited from medical clinics and school health classes in low-income neighborhoods of Birmingham, Alabama, that had high rates of unemployment, substance abuse, violence, STDs, and teenage pregnancy. Results: Of the 522 adolescents enrolled in the trial, 92% (n = 479) completed baseline STD testing and follow-up surveys. At baseline, 28% had positive test results for at least one disease: 4.8 % for Neisseria gonorrhoeae, 17.1% for Chlamydia trachomatis, and 12.3% for Trichomonas vaginalis. Of the adolescents with negative STD test results, 98.8% were accurate in their self. report of STD status, as compared with 68.7% of the adolescents with positive results. Underreporting varied by type of STD. Adolescents who accurately reported their positive STD status were significantly more likely to report their receipt of treatment accurately (P < 0.001). Conclusions: The substantial underreporting of STD incidence in this study suggests that reliance on self-reports of STD history may introduce misclassification bias, potentially leading to false conclusions regarding the efficacy of prevention interventions. This observation highlights the importance of using biologic indicators as outcome measures.