The effects of repeated cervical infections followed by a single direct tubal inoculation with Chlamydia trachomatis, serovars D and F, were examined in 11 pig-tailed macaques to test the hypothesis that tubal inoculation after cervical priming causes a more severe disease than primary tubal inoculation alone. Animals were cervically inoculated between two and five times. Fallopian tubes were inoculated with serovar D or F 1 week after the last cervical challenge. Three control monkeys received only one direct tubal inoculation without previous cervical inoculation. Infection was confirmed by isolating the microorganism from the endocervix in 13 of 14 monkeys and from the endosalpinx in four only after the tubal inoculation. Antibody was detected in post-infection sera of all 14. Tubal edema occurred in seven of 11 animals after the first cervical inoculation, and uterine erythema occurred in 11 of 11 after the second cervical inoculation. Peritubal adhesions were induced before the tubal inoculation in zero of seven given three or fewer cervical inoculations and four of four given five cervical inoculations (P less than .01). After direct tubal inoculation, peritubal adhesions became more prominent, and the 11 hysterectomy specimens showed plasma cell endometritis in nine and salpingitis in nine. Two control monkeys developed minor adhesions, the other none. One tube in two of three controls showed mild plasma cell infiltrates, whereas no evidence of endometritis was observed in controls. Histopathology in these monkeys was characteristic of chlamydial endometritis and salpingitis. However, the pathogenesis of these changes is uncertain because C trachomatis was not isolated from the endosalpinx after cervical inoculations alone.