Intercellular adhesion molecule-1 (ICAM-1), a member of the immunoglobulin supergene family, is known to play an important role in inflammatory diseases. Using a previously developed enzyme-linked immunosorbent assay (ELISA) with two monoclonal antibodies (MoAbs) against human ICAM-1, levels of soluble ICAM-1 (sICAM-1) were measured in sera from patients with collagen diseases and in synovial fluids (SF) from patients with rheumatoid arthritis (RA). Although the results did not demonstrate that RA and other collagen diseases, as a group, had significantly higher levels of sICAM-1 in sera as compared with healthy controls, 21 of 138 cases (15%) with collagen diseases and 11 out of 57 patients (19%) with RA clearly showed higher levels of sICAM-1 in the sera. Comparisons between RA patients of radiological stages I and II and between stage I and other stages showed significantly higher levels of sICAM-1 in the sera of patients in the latter stages. RA patients with vasculitis and/or pneumonitis showed significantly higher levels of sICAM-1 than those without vasculitis or pneumonitis. Significant correlations were demonstrated between sICAM-1 and the factors IgG-RF, IgM-RF, erythrocyte sedimentation rate (ESR) and TNF-alpha in sera of RA patients. In addition, it was noted that the levels of sICAM-1 in SF were as high as those in the sera of patients with RA.