Adhesion molecules are critically involved in inflammatory responses. We studied serum concentrations of the soluble form of E-selectin (endothelial-leukocyte adhesion molecule-1, ELAM-1) in 187 patients with neuropathies of diverse etiology, 54 patients with other noninflammatory, nondemyelinating neurologic disorders, and 15 healthy controls. Serum E-selectin levels, quantitated by a two-site enzyme-linked immunosorbent assay, were significantly increased in 126 patients with Guillain-Barré syndrome (GBS) (mean +/- SD, 45.1 +/- 16.3 ng/ml) and 13 patients with vasculitic neuropathies (47.1 +/- 19.1ng/ml) compared with patients with other neurologic diseases (19.8 +/- 7.4 ng/ml) and healthy controls (21.9 +/- 8.1 ng/ml). In GBS, E-selectin levels were temporally related to disease activity. Cytokine-mediated upregulation of E-selectin may be important in homing and attachment of leukocytes to endoneurial endothelial cells. Raised E-selectin concentrations probably reflect endothelial cell activation occurring early in the sequence of immunopathologic events culminating in peripheral nerve damage.