Genital Chlamydia trachomatis infections often result in pelvic inflammatory disease and sequelae including infertility and ectopic pregnancies. In addition to the already established murine models, the development of other animal models is necessary to study the safety and efficacy of prototype vaccine candidates. The intravaginal infection of guinea pigs with C. trachomatis has been tested in three independent studies. The first two studies investigated the effect of hormonal treatment of the animals prior to infection with serovars D and E. The results showed that estradiol treatment was required for sustained infection. The third study conducted an immunization-challenge experiment to explore the feasibility of measuring protection in this guinea pig model. C. trachomatis bacteria were sampled using vaginal swabs and measured by qPCR. Using immunohistochemistry the bacteria were detected in the oviducts 19 days post-infection, indicating that the estradiol treatment resulted in ascending infection. Furthermore, immunization of guinea pigs with live EB formulated with ISCOM matrix led to reduction of cervico-vaginal shedding and diminished the severity of pathology. In this study we have developed a new guinea pig model of C. trachomatis female genital tract infection for the purpose of evaluating potential vaccine candidates. © 2011 Elsevier Ltd.