Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of diseases characterized by chronic inflammation of muscles. We investigated the role of cellular adhesion molecules implicated in the cohesion of endothelial cells in IIM. In 22 patients with IIM we investigated plasma concentrations of soluble junctional adhesion molecules [platelet-endothelial cell adhesion molecule (sPECAM-1) and sCD146] and cellular adhesion molecules [sP-selectin, sE-selectin, intercellular adhesion molecule (sICAM-1), and vascular cell adhesion molecule (sVCAM-1)] implicated in leukocyte/endothelial cell interactions. Results were compared to a control group. Muscle biopsy samples from 8 out of 22 IIM patients were studied by immunohistochemistry for tissue expression of these molecules and compared to normal muscle samples. PECAM-1 and CD146 expression was also studied using immunoblots from muscle biopsies from 5 patients and 2 controls. We observed distinct patterns of soluble levels and in situ expression between dermatomyositis (DM), polymyositis (PM), and sporadic inclusion body myositis (s-IBM). PM samples showed significantly increased levels of sCD146, sPECAM-1, and s-ICAM1 and increased expression of CD146, CD31, and ICAM-1 in endothelial cells, whereas CD146 and ICAM-1 were also recorded in some muscle fibers. In DM, sE-selectin, sP-selectin, and sPECAM-1 were significantly increased, with abnormal expression of ICAM-1 in endothelial cells and perifascicular muscle fibers. In the small group of s-IBM samples, results were similar to PM, but the only significant increase was the level of sPECAM-1. Immunoblots confirmed increased expression of PECAM-1 and CD146 in all IIM muscles in comparison to controls, with the highest expression in PM and IBM samples. We observed abnormal increases of soluble levels of adhesion molecules implicated in endothelial cell junctions in PM (sCD146, sPECAM-1) and to a lesser extent in DM and s-IBM (sPECAM-1). We conclude that the distinctly different profiles between PM/s-IBM and DM reflect differences in the pathophysiological background of these diseases.