PURPOSE: Trachoma remains a leading cause of blindness. Determining the most effective antibiotic treatment strategy is essential for the success of country-based trachoma control programs. METHODS: Baseline and 2-month follow-up examinations were performed in a trachoma-hyperendemic village. All residents were offered azithromycin for trachoma after baseline was determined. Infection with Chlamydia trachomatis and chlamydial load were determined by PCR. Clinical trachoma status was evaluated. A high chlamydial load was defined as a higher than median chlamydial load among those with infection. Risk factors were examined in multiple logistic regression models. Associations are presented as odds ratios and 95% confidence intervals. RESULTS: At baseline, 57% of participants were infected with C. trachomatis. Although clinical trachoma correlated with infection, 23% of participants with high chlamydial loads showed no clinical signs. Adults represented only 10% of the population with high loads. Treatment significantly decreased the proportion positive in the community and the load in the community. However, 27% of individuals with high loads at baseline who received treatment also were infected at 2 months. Of those, 93% with high loads at 2 months were aged < or =10 years. CONCLUSIONS: Although most of the chlamydial load in this community resided in children, 10% of the high load resided in adults, most of whom did not have follicular trachoma and in whom the infection would be missed under treatment strategies that focus on clinical disease or children. These data support a mass treatment strategy for hyperendemic communities, at least as a first approach. In addition, treatment of children age < or =2 years should be reexamined, as >30% with high loads at baseline remained infected at 2 months, despite monitored treatment according to weight.