Context: The World Health Organization recommends mass antibiotic distributions in its strategy to eliminate blinding trachoma as a public health concern. Some hypothesize that a single distribution is sufficient to control the ocular strains of chlamydia that cause trachoma. Others believe infection will inevitably return and periodic treatments or other measures are essential. Objective: To determine whether ocular chlamydial infection returns to the community up to 24 months after a single mass antibiotic distribution in a hyperendemic region of Ethiopia. Design, Setting, and Participants: Longitudinal cohort study conducted March 2003 to March 2005 in the Gurage Zone of Ethiopia. Eight randomly selected villages were assessed for ocular chlamydial infection. Fifteen untreated villages were randomly chosen at 12 months to allow assessment of a secular trend. Intervention A single dose of oral azithromycin was offered to all residents of the 8 selected villages who were aged 1 year or older. Main Outcome Measure: Prevalence of ocular chlamydial infection in all children aged 1 to 5 years from each intervention village prior to treatment and 2, 6, 12, 18, and 24 months after mass antibiotic treatment, and also in untreated villages enrolled at 12 months. Results: Five hundred fifteen children were examined for ocular chlamydial infection at baseline. For the followup examinations, the mean participation rate was 83% . The mean prevalence of infection in children aged 1 to 5 years decreased from 43.5% (95% confidence interval [CI]35.0% - 52.0% ) to 5.1% (95% CI, 1.1% - 9.2% ) after treatment. On average, infection returned gradually over 24 months to 11.3% (95% CI, 4.5% - 18.1% ; P=.001). In 7 of 8 villages, infection was higher at 24 months than at 2 months. In the remaining village, no infection could be identified at any point after treatment. Villages enrolled at 12 months had significantly fewer infections than those enrolled 12 months earlier, suggesting a secular trend (P< .001). Conclusions: Ocular chlamydial infection was not eliminated in children aged 1 to 5 years after a single mass azithromycin distribution; it slowly returned over 24 months, although not to baseline levels. Repeated treatments or other effective measures will be necessary for elimination. Context: The World Health Organization recommends mass antibiotic distributions in its strategy to eliminate blinding trachoma as a public health concern. Some hypothesize that a single distribution is sufficient to control the ocular strains of chlamydia that cause trachoma. treatments or other measures are essential. Objective: To determine whether ocular chlamydial infection returns to the community up to 24 months after a single mass antibiotic distribution in a hyperendemic region of Ethiopia. Design, Setting, and Participants: Longitudinal cohort study conducted March 2003 to March 2005 in the Gurage Zone of Ethiopia. Eight randomly selected villages were assessed for ocular chlamydial infection. Fifteen untreated villages were randomly chosen at 12 months to allow assessment of a secular trend. Intervention A single dose of oral azithromycin was offered to all residents of the 8 selected villages who were aged 1 year o Main Outcome Measure: Prevalence of ocular chlamydial infection in all children aged 1 to 5 years from each intervention village prior to treatment and 2, 6, 12, 18, and 24 months after mass antibiotic treatment, and also in untreated villages enrolled For the followup examinations, the mean participation rate was 83%. The mean prevalence of infection in children aged 1 to 5 years decreased from 43.5% (95 % confidence interval [CI] 35.0% -52.0%) to 5.1% (95% CI, 1.1% -9.2% In the remaining village, no infection could be identified at any point after treatment. Villages enrolled at 12 months had more fewer infections than those enrolled 12 months earlier, suggesting a secural trend (P <.001). Conclusions: Ocular chlamydial infection was not eliminated in children aged 1 to 5 years after a single mass azithromycin distribution; it slowly returned over 24 months, although not to baseline levels. Repeated treatments or other effective measures will be necessary for elimination.