Genital chlamydia is a public health concern. The World Health Organization (WHO) estimates that 90 million of all new cases of sexually transmitted diseases (STDs) per year are caused by Chlamydia (C.) trachomatis. In the United States alone, approximately 3 million new cases of chlamydia are reported yearly, and the costs associated with their management and complications exceed $2 billion. Unfortunately, at least 75 percent of females with chlamydia are asymptomatic, and unless the infection is detected through chlamydia testing (screening), their infection may be transmitted to others or lead to complications. The Centers of Disease Control and Prevention (CDC) recommends either azithromycin 1 gram (gm) by mouth (PO) once or doxycycline 100 milligrams (mg) PO twice daily (BID) for 7 days as co-equal therapies for uncomplicated chlamydia. A secondary aim will be to determine demographic predictors of chlamydia treatment failure following azithromycin or doxycycline treatment, and to explore clinical parameters, which distinguish those with persistent infection. The study design of this Phase III trial will address major limitations of prior chlamydia efficacy studies and the findings will reveal both the true efficacy of azithromycin and doxycycline in uncomplicated chlamydia in adolescents and the factors that predict treatment failure. This study is designed primarily to determine the frequency of chlamydia treatment failure following either azithromycin or doxycycline regimens and to evaluate whether the efficacy of the azithromycin regimen is inferior to the doxycycline regimen. Both drugs are Food and Drug Administration (FDA) approved for use in the U.S. The study will enroll 650 males and females age 12-21 years in good health (based on vital signs and provider's clinical evaluation documented in medical records) who are residing in long-term gender-segregated (not co-ed) youth correctional facilities (YCFs) (usual stay \>3 weeks) and who are identified as chlamydia-infected would comprise the study population until 306 evaluable subjects are obtained . Only individuals who have a positive chlamydia screening test are enrolled, and those with negative screening tests are excluded. Consenting chlamydia-positive subjects at the enrollment visit (study visit 1) will be enrolled, asked to provide demographic data, to provide a first-void urine sample (not a mid-stream specimen) for repeat chlamydia testing with Gen-Probe (GP) AC2 (for verification of chlamydia), and then randomized to 1 of 2 treatment arms (190 153 subjects per arm): doxycycline 100 mg PO BID for 7 days or azithromycin 1 gm PO single dose. Both therapies are given as directly observed, and side effects are evaluated at the first follow-up visit (day 28 after study drug initiation). If a subject who's GP AC2 from the enrollment treatment visit returns negative for C. trachomatis, they will be categorized as unevaluable and will be removed from the study, then the site investigator will determine whether the subject will complete this treatment or will receive other therapy. Subjects whose GP AC2 at the enrollment treatment visit is positive for C. trachomatis will then be asked to provide a first-void urine sample for repeat chlamydia testing with GP AC2 at 28- and 67-days after study drug initiation \[corresponding to the first follow-up visit (study visit 2) and second follow-up visit (study visit 3), respectively\].