Fibronectin, a high molecular weight glycoprotein that binds to glycosaminoglycans, fibrinogen or fibrin, and collagen, was identified and quantitated in synovial fluid from patients with various rheumatic diseases. Fibronectin concentration was significantly higher in synovial fluids from patients with rheumatoid arthritis (RA) (697 microgram/ml) than in other synovial fluids. In RA, synovial fluid fibronectin concentration exceeded that in plasma and did not directly correlate with synovial fluid concentrations of albumin, total protein, or fibrinogen. Synovial fluid fibronectin concentration correlated directly with synovial fluid white blood cell count (r = 0.50, P less than 0.005). Fibronectin was present in cryoprotein formed from four rheumatoid synovial fluids.