The host immune response contributes to the pathology of C. trachomatis infection of the genital tract. Low grade, chronic, or persistent infection may contribute to pathology by eliciting an ongoing chronic immune response. Prior studies in our laboratory found PCR evidence for persistence of chlamydial DNA in endocervical swabs obtained from mice up to 60 days post resolution of active infection as determined by culture. The objective of this study was to determine whether persistent infection could be prevented by doxycycline treatment early in the course of infection (10-24 days), or if late doxycycline treatment (days 42-56) would eradicate persistent organisms. In the group that received early antibiotic treatment, active infection resolved by day 14, and in the groups that received no antibiotic or were treated late, active infection resolved by day 28. Nested PCR revealed evidence for chlamydial DNA thru day 88 in all three groups. Unilateral or bilateral oviduct hydrosalpinx developed in 69% of mice that received no antibiotic treatment or were treated early, and in 50% of mice in the late treatment group, p = .44. Thus, antibiotic treatment was unable to prevent persistent infection whether given during the acute or chronic phase. Persistent infection may contribute to oviduct pathology, or a robust early inflammatory response may be all that is necessary to induce chronic oviduct pathology.