Guinea pigs were infected intravaginally with the chlamydial agent of guinea pig inclusion conjunctivitis at varying times during the estrous cycle. Genital tract tissues were collected 30 days after infection and processed for histopathological analysis. No difference was seen in the course of lower genital tract infection. However, a significantly greater percentage of tissues from animals infected on day 11 of the cycle were found to have chronic inflammation and fibrosis in the mesosalpinx compared to those from animals infected on day 6 or day 16. In addition, a significantly greater percentage of oviduct tissues from day 11-infected guinea pigs had marked tubal dilatation when compared to oviducts from day 6-or day 16-infected animals. The increased incidence of pathological changes was also noted in the endocervix, uterine fundus, and uterine horns but not the exocervix. These data indicate that the time of the estrous cycle and the corresponding hormonal influences may be an important influence on the development of upper genital tract disease.