We studied interleukin-10 (IL-10) levels in the blood and synovial fluid (SF) of 15 patients with RA and in the blood of 15 healthy donors (HD). RA IL-10 levels were significantly higher in SF than in blood (p = 0.001) and did not correlate with the disease activity nor with the therapy. RA patients showed significantly reduced blood IL-10 levels compared to the HD (p = 0.002), suggesting that IL-10 synthesis is depressed in RA. Since IL-10 has anti-inflammatory properties, reducing pro-inflammatory cytokine release by monocytes and down-modulating T cell function, its defect in RA may play a role in perpetuating RA synovitis.