Recent studies have shown that the urogenital pathogen Chlamydia trachomatis to be a major bacterium triggering reactive arthritis (ReA), and is able to induce interleukin-6 (IL-6) production in human fibroblast-like synovial cells (FSC) in vitro. In the present study, we examined the correlation between IL-6 production and multiplication of chlamydia in FSC. All FSC from five patients secreted highly increased quantities of IL-6 in a dose-dependent and time-dependent fashion. Heat and UV inactivated chlamydia failed to enhance production of IL-6. When azithromycin was added to infected cultures of FSC at 0 or 48 h after infection, the level of IL-6 production was very low. Transmission electron microscopy of such infected cultures revealed many abnormal forms of chlamydia within the inclusions in FSC. From one step-growth curve experiments, it was suggested that C. trachomatis hardly multiplied in FSC. In contrast, in C. trachomatis infected HeLa 229 cells, chlamydia multiplied as usual, but little IL-6 production were found. These observations indicated that live chlamydia and the persistence of chlamydia may be essential for stimulating the synthesis of IL-6 in FSC.