Major outer membrane protein sequences, determined from Chlamydia-positive eye swab samples collected in 2 Egyptian villages, were used to analyze the epidemiology of trachoma in an endemic setting. Samples were collected during the 1999 Azithromycin in Control of Trachoma trial, in which residents of villages were mass treated with either oral azithromycin or topical tetracycline and were followed up for nearly 2 years. Three genovar families (A, Ba, and C) and 12 genovars were detected, with 2 genovars (A1 and Ba1) comprising almost 75% of the samples. The presence of >1 genovar within households was common, with > or =24% of households having >1 genovar. Evidence consistent with reinfection and persistence as mechanisms of communitywide continued presence of trachoma was provided by data for individuals infected with rare genovars.