Immunohistological analysis of tissue sections from human brain revealed that intercellular adhesion molecule-1 (ICAM-1) is mainly expressed on endothelial cells of small vessels, including the subependymal vessels of the choroid plexus. In addition, it is expressed on cerebrospinal fluid (CSF) cells in patients with inflammatory diseases of the central nervous system. Stimulation of confluent monolayers of adult human cerebral endothelial cells with lipopolysaccharide (LPS) or recombinant human tumor necrosis factor-alpha (TNF-alpha) could induce expression and secretion of soluble ICAM-1 in a dose dependent manner. In addition, sICAM-1 was also present in the supernatant from U251 glioma cells. No sICAM was detected in the culture supernatant from activated blood or CSF lymphocytes. Cerebral endothelial cells are therefore a likely source for sICAM-1 in the CSF.