We investigated the in vitro adhesion of 51Cr-labeled lymphocytes to cultured brain endothelial cells and the in vivo expression of intercellular adhesion molecule-1 (ICAM-1) on cerebral endothelial cells in a rat model of experimental allergic encephalomyelitis (EAE) before and after treatment with lipopolysaccharide (LPS). Adhesion of lymphocytes to cerebral endothelial cells was significantly increased in EAE compared with controls (p < 0.01), and was significantly correlated with the percentage of major histocompatibility complex class II antigen-positive cells in lymph node cells (p < 0.001). LPS enhanced ICAM-1 expression on endothelial cells and lymphocyte adhesion to those cells, and caused a significant increase in the in vivo expression of ICAM-1 compared with controls (p < 0.001). Lymphocyte adhesion to endothelial cells was significantly blocked by monoclonal antibodies against ICAM-1, lymphocyte function-associated antigen-1, or very late activation antigen-4. Our findings suggest that lymphocyte adhesion to brain endothelial cells may contribute to lymphocyte migration across the blood-brain barrier in EAE and that LPS may cause progression of EAE lesions.