We compared a single 1 gm dose of azithromycin with the standard 7-day course of doxycycline for the treatment of uncomplicated chlamydial genital infection in sexually active adolescents. Seventy-three adolescents (65 female) with a cervical or urethral culture positive for Chlamydia trachomatis were enrolled in the study; 46 received azithromycin and 27 received doxycycline. Follow-up evaluations were done 1, 2, and 4 weeks after treatment with azithromycin or initiation of treatment with doxycycline. There were four treatment failures (8.7%) among the patients who received azithromycin and four in the doxycycline-treated group (14.8%); all were female. Six of these girls (three treated with azithromycin and three with doxycycline) gave histories of unprotected intercourse with an untreated partner and were probably reinfected. Almost half the patients were clinically symptom free. The clinical response rate for the remaining patients with symptoms was 97.4% at 4 weeks. Nineteen percent of the azithromycin-treated patients and 33.3% of those treated with doxycycline had mild to moderate drug-related side effects, which were predominantly gastrointestinal. We conclude that treatment with a single oral dose of azithromycin appears to be as safe and efficacious as a 7-day course of doxycycline for the treatment of uncomplicated genital chlamydial infection in adolescents.