Immune responses to Chlamydia trachomatis infection in trachoma do not protect against reinfection or the development of scarring and blindness. In addition, the immunoregulatory contribution of cytokines to the development of conjunctival histopathology or protection is undefined. In this study, conjunctival cytokine mRNA transcripts were compared among subgroups of chlamydia infection status and ocular disease presentations of 50 individuals from an area where trachoma is endemic. There was a significant association of elevated interleukin (IL)-1beta, transforming growth factor beta1, and tumor necrosis factor alpha transcripts with infection, follicular inflammation, and scarring. Both gamma interferon (IFN-gamma) and IL-2 transcripts were significantly associated with infection; slightly elevated IL-2 levels were found in inflammatory disease. High IFN-gamma transcript levels were present with follicles and inflammatory disease and to a lesser extent with inflammatory scarring. The role of IFN-gamma in protection from infection or disease was not apparent from this study, since transcripts were frequently present in both chlamydial infection and disease. IL-12 (p40) transcripts were elevated in adults and children in association with follicular inflammation but not with scarring. IL-4, IL-5, and IL-10 transcripts were not detected in any samples. In conclusion, C. trachomatis infection stimulates local cytokines which favor a strong cell-mediated and proinflammatory response in both the early and later manifestations of trachoma. In addition, cytokine transcript levels that were associated with disease but no infection were characteristically lower overall than when chlamydia was present.