A controlled double-blind stratified trial was carried out in a village in Southern Iran to assess the efficacy of family-based intermittent therapy of hyperendemic trachoma with topical oxytetracycline oily suspension twice daily for 7 days each month, or oral doxycycline 5 mg per kilogram of body weight once a month, in comparison with a control group which received vitamin pills once a month. In addition all other members of the selected children's families were also treated with the same regimen of therapy. The treatment was given for a period of 1 year by 3 field technicians, each responsible for one regimen of therapy. Examining the whole conjunctiva 4 months after the start of therapy, we observed no marked difference in the cure rate or the number of patients with moderate to severe trachoma between the groups treated with antibiotics and the control group. When treatment was continued for 12 months, a marked decrease in the prevalence of trachoma and in the grades of intensity of inflammatory responses as well as the positivity rate for Chlamydia trachomatis was observed in the groups treated with the topical oxytetracycline or oral doxycycline compared with the control group. While there was no marked difference between the efficacy of these 2 regimens of mass chemotherapy, the monthly intermittent therapy with a single dose of doxycycline offers the advantage of being more practical and less expensive for mass control of trachoma by requiring approximately one-tenth of the staff, transport, and other facilities required for the intermittent topical therapy with tetracycline eye ointment.