Synovial fluid (SF) mononuclear cells (MNC) from 13 patients with rheumatoid arthritis (RA) and 12 patients with other arthritic diseases (OD) including osteoarthritis (OA), gout and spondyloarthritis (SA) were cultured in the presence of collagen types I and II or lipopolysaccharide (LPS) for 24 h. Interleukin-1 (IL-1), IL-6 and tumor necrosis factor-alpha (TNF-alpha) in the SF and culture supernatants were assayed using ELISA. The results showed that one-half of the RA patients with high SF monocyte count had high SF IL-6 levels that coincided with the high spontaneous release of IL-6 by SF MNC. In the other RA patients with lower SF monocyte count, type II collagen induced significantly higher IL-1 beta than the medium control levels by SF MNC (P < 0.01) or that of the other diseases (P < 0.01). Similarly, type II collagen-induced IL-6 and TNF-alpha production rose significantly (P < 0.01) from SF MNC of RA but less from OD (P < 0.05). In addition, type I collagen could also induce IL-1, IL-6 and TNF-alpha in these samples from RA and OD patients but was less potent than type II collagen. Our results indicate that collagen-induced cytokines may be important in the pathogenesis of the disease.