Intercellular adhesion molecule ICAM-1 has a crucial role in the induction of an immune response and is instrumental in migration of T cells into inflamed tissue. We studied soluble ICAM-1 concentrations in patients with multiple sclerosis (MS), viral encephalitis, and other immunologic diseases, and compared results with those in other noninflammatory, nondemyelinating neurologic disorders as well as in healthy controls. MS patients with clinically active disease or enhancing lesions on MRI had elevated serum levels of soluble ICAM-1. Concentrations of soluble ICAM-1 were also increased in some patients with viral encephalitis. These findings raise the possibility that circulating ICAM-1 serves as a marker of acute inflammatory events in the brain and add to evidence implicating this adhesion molecule in the pathogenesis of MS.