To investigate differences in helper T cell immune responses in cerebrospinal fluid (CSF) between neuromyelitis optica (NMO) and multiple sclerosis (MS), we measured CSF levels of interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor-a and interferon-c at the time of relapse in 17 NMO patients and 21 MS patients using fluorescence-activated cell sorting. CSF IL-6 levels were significantly higher in NMO patients than in patients with MS (P = 0.001) and other neurological diseases (P = 0.001). The other cytokines tested were undetectable. Elevated CSF levels of IL-6 in only NMO supports the view of different pathophysiologies of NMO and MS. CSF IL-6 levels may be useful in the differential diagnosis of the two disorders.