Multiple sclerosis (MS) is an inflammatory demyelinating disorder of the central nervous system (CNS). Natalizumab ((R)Tysabri) is a humanized recombinant monoclonal antibody that binds to the alpha (alpha)(4) chain of the alpha(4) beta (beta)(1) integrin (very late activation antigen 4; VLA-4), and alpha(4)beta(7) integrin. Recently, two patients with MS and one patient with Crohn's disease who were treated with natalizumab in the setting of clinical trials developed progressive multifocal leukoencephalopathy (PML), an opportunistic infection of the brain with the polyoma virus JC. We recently showed that natalizumab decreases the numbers of CD4(+) and CD8(+) T lymphocytes, CD19(+) B cells, and CD138(+) plasma cells in the cerebrospinal fluid (CSF) of patients with MS on natalizumab therapy. In addition, we demonstrated that the cell numbers in CSF remained unchanged even 6 months after cessation of natalizumab treatment.