T he basic mechanisms underlying reactive arthritis and specifically the joint injury that follows intra-articular Chlamydia trachomatis infection have not been defined. The present study addresses this question through the development of an experimental model. Stable cell lines were generated from synoviocytes harvested from the knee joints of Lewis rats. The synoviocytes were cocultivated with C. trachomatis to allow invasion by the microbe and were then transferred by intra-articular injection into the knee joints of Lewis rats. The ensuing arthritis could be subdivided into an early phase (</= 14 d) and a late phase. The early phase was characterized by intense, primarily neutrophilic, synovitis; accelerated cartilage injury; dissemination of Chlamydia to liver and spleen; and viable Chlamydia in the joints. The late phase was marked by mixed mononuclear lymphocyte infiltration in the joint; dysplastic cartilage injury and repair; absence of viable organisms; and development of a distinctive humoral response. Western blot analysis comparing reactive arthritis patients to the experimental model indicates that candidate arthritogenic chlamydial antigens are comparable between the two. This model demonstrates that an intense synovitis can be induced by this intracellular pathogen, and that chronic inflammation can persist well beyond the culture-positive phase. Furthermore, these data show that the synoviocyte is a suitable host cell for C. trachomatis and can function as a reservoir of microbial antigens sufficient to perpetuate joint injury.