We simultaneously measured the concentrations of parathyroid hormone related peptide (PTHrP) and cytokines in synovial fluid (SF) to clarify the relationship between PTHrP and cytokine network in the SF of elderly patients with arthritis. SF was collected from knee joints of five RA patients aged 66±11 years old and nine osteoarthritis (OA) patients aged 80±9 years old. PTHrP in SF was measured by enzyme-linked immunosorbent assay (ELISA), whereas tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6) and interleukin-8 (IL-8) in SF were all measured by ELISA. The PTHrP levels in the SF of RA patients (2.56±0.89pmol/l) were significantly (p<0.05) higher than those of OA patients (1.66±0.17pmol/l). TNF-α, IL-1β, IL-2 and IL-6 concentrations in SF of RA were also significantly higher than those in SF of OA (TNF-α 22.5±14.8vs 4.8±3.0pg/ml, p<0.01; IL-1β 11.8±11.4vs 1.4±1.3, p<0.05; IL-2 59.9±46.6vs 12.5±8.0pg/ml, p<0.05; IL-618424±8901vs 3547±2948pg/ml, p<0.01). The concentrations of IL-4 and IL-8 in SF of RA were similar to those of OA. Immunohistochemical studies revealed the presence of immunoreactive PTHrP in synovial fibroblasts from RA and OA. Among cytokines, only IL-6 was positively correlated with PTHrP levels in SF(r=0.685, p<0.01). In the culture of synovial cells from RA and OA, PTHrP was produced in RA more than OA after phorbol 12-mysistate 13-acetate (TPA) stimulation. These results indicate that PTHrP and cytokines, especially IL-6, might be involved in the inflammatory processes of elderly RA and OA. This is the first study in which PTHrP and cytokine levels were simultaneously examined in synovial fluid of elderly RA and OA.