Elderly-onset rheumatoid arthritis (EORA) is thought to be different from younger-onset disease (YORA) for many reasons, including a more elevated acute phase response and a more abrupt onset; both events are mainly regulated by pro-inflammatory interleukins (ILs), in particular, IL-1, IL-6 and IL-8. To compare the synovial fluid (SF) levels of these ILs, and their relationship to local inflammation as well as the acute phase response, erythrocyte sedimentation rate (ESR) and serum C-reactive protein (CRP) in the two RA subsets, we determined white blood cell (WBC) number, total protein (TP), IL-1beta, IL-6 and IL-8 concentrations in the SF of 50 patients, 15 with EORA and 35 with YORA. Both ESR and CRP were higher in EORA than in YORA. IL-6 was higher in SF of EORA (2111.37 +/- 1425.03 pg/mL) than YORA (1077.53 +/- 757.62 pg/mL, p = 0.002), while no difference was observed for SF IL-1beta and IL-8. There was a weak correlation between SF IL-6 and IL-1beta in EORA, whereas SF ILs and CRP and/or ESR did not show any correlation in both groups. Our study indicates that in EORA, as in other diseases occurring in the elderly, there are elevated levels of IL-6. Higher SF levels of IL-6 may be, at least in part, responsible for the different behavior of EORA with respect to YORA.