Cellular adhesion molecules, such as E-selectin, function to recruit leukocytes into inflammatory lesions. Recently, a soluble form of this adhesion molecule, sE-selectin, has been described. In this study we determined soluble E-selectin (sE-selectin) in synovial fluid (SF) and blood samples from patients with rheumatoid arthritis (RA) and other inflammatory disorders and correlated sE-selectin levels with clinical parameters of disease activity. SF, blood, and cells isolated from RA SFs and synovial tissues (STs) were examined from 76 patients. In addition, normal plasma as well as supernatants from cultured human umbilical vein endothelial cells (HUVECs) were obtained. sE-selectin levels were assayed in these fluids and cell supernatants by an enzyme-linked immunoabsorbant (ELISA) assay. SFs from patients with RA had significantly higher sE-selectin levels than did those from osteoarthritis (OA) SFs (P < 0.05). SF sE-selectin levels were correlated with SF leukocyte counts. HUVECs, or RA ST cells enriched in endothelial cells, produced sE-selectin. Neutrophils isolated from RA SFs did not release sE-selectin. SF soluble intercellular adhesion molecule-1 levels correlated positively with sE-selectin levels. We conclude that sE-selectin levels are increased in SFs from RA compared to those from OA. Endothelial cells derived from umbilical vein or from RA STs release sE-selectin. Thus, sE-selectin may be important in the migration of inflammatory leukocytes into diseased RA STs and SFs.