We examined the production of substance P (SP) in synovial fibroblasts derived from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Immunoreactive SP was observed in non-stimulated RA fibroblasts. The expression of β-preprotachykinin-A (β-PPT-A) mRNA was confirmed by reverse transcription-polymerase chain reaction analysis. SP contents in culture medium were increased by treatment of RA fibroblasts with transforming growth factor-β (TGFβ) (10 ng/ml). Levels of SP release were elevated at 12 h after TGFβ stimulation whereas the expression of β-PPT-A mRNA was enhanced at 3 h. Furthermore, SP production in response to TGFβ was dose-dependently enhanced by basic fibroblast growth factor (bFGF). OA fibroblasts also significantly released SP in the presence of TGFβ (10 ng/ml) plus bFGF (50 ng/ml). These results suggest that SP produced by synovial fibroblasts may participate in joint diseases.