Trachoma, an infectious keratoconjunctivitis caused by Chlamydia trachomatis, is a leading cause of preventable blindness in developing countries. In this study we compared oral azithromycin with oxytetracycline/polymyxin eye ointment (once daily for 5 days every 4 weeks; total of six treatment cycles) for the treatment of active endemic trachoma in 168 rural Egyptian children. A suspension of azithromycin was administered to children as a dose of 20 mg/kg by one of three schedules: a single dose, one dose a week for 3 weeks, and one dose every 4 weeks for a total of six doses. The children's clinical status and chlamydial infection rates were evaluated for 1 year. The clinical cure rates were 35% 2 months after initial treatment, 16% at 8 months (during the annual autumn epidemic of purulent conjunctivitis), and 47% at 1 year. The pretreatment chlamydial infection rate of 33% (determined by direct immunofluorescence) decreased to 5% at 2 months and was 9% at 12 months. There were no significant clinical or laboratory differences among the four treatment groups. Thus, 1-6 doses of azithromycin were equivalent to 30 days of topical oxytetracycline/polymyxin ointment and may offer an effective alternative means of controlling endemic trachoma.