The immediate study objective was to determine if variable disease severity in children with trachoma could be attributable in part to host variation in the ability to clear Chlamydia trachomatis infection. Identification of sibling cohorts with these variant phenotypes would be useful for immunogenetic studies. A weekly survey for 3 months in a trachoma-hyperendemic village using detection of chlamydial DNA and grading of disease severity indicated that 62% (33/53) of children had at least one infection episode. Of those, 64% (21/33) who were persistently infected had both significantly higher mean chlamydial DNA loads and more severe trachoma than did sporadically infected children. Of importance, duration of infection differed between siblings in 60% (6/10) of families. The results suggest that chlamydial load and duration of infection determine the chronic nature of severe disease in trachoma and that host variable efficiency for chlamydial clearance between siblings is in part determined by host variation.