Adhesion molecules are essential mediators for lymphocyte trafficking through the blood-brain barrier into the CNS in multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). However, the role of the selectin molecules and their ligand, P-selectin glycoprotein-1 (PSGL-1) which mediates tethering and rolling of the leukocytes in demyelinating disease remains controversial. This study demonstrates that mice deficient in PSGL-1 are not significantly different in the development and progression of EAE compared to wild type controls. Our observations suggest that PSGL-1-selectin interactions are redundant and not required for the development of EAE. Our data also indicate that other adhesion molecules are necessary for the initial rolling events leading to leukocyte infiltration into the CNS during EAE.