Relapsing Devic's neuromyelitis optica (DNO) may be clinically undistinguishable from multiple sclerosis (MS), thus the differential diagnosis relies mainly on neuroimaging and cerebrospinal fluid (CSF) findings. We studied CSF samples from 44 patients with DNO submitted to at least one lumbar puncture. Pleocytosis, IgG synthesis and blood brain barrier damage were the most frequent abnormalities, pleocytosis being very suggestive of DNO in patients fulfilling clinical and MRI diagnostic criteria. Pleocytosis > or =50 cells/mm3 is more frequent in the active phases of the disease. Oligoclonal bands (OBs) should be re-considered within the diagnostic criteria of DNO for possible variations in time: at variance with MS they may also disappear. Thus, more than one CSF examination should be done in the presence of suspected DNO, preferably in different disease phases. Although uncommon, OBs do not exclude DNO if optic nerve and spinal cord are the only sites of white matter damage, provided that cerebral MRI is normal at onset and during follow up.