Sixteen cerebrospinal fluid (CSF) specimens serially obtained during long-term follow-up of two patients with Devic's neuromyelitis optica (DNO) were compared with 65 CSF samples from patients with multiple sclerosis (MS). By statistical analysis, the CSF profile in DNO was found to differ from that observed in MS, mainly showing pleocytosis, blood-brain barrier damage, and absence of persistent immunoglobulin G synthesis within the central nervous system. Oligoclonal bands, detected with isoelectric focusing, were present in CSF of 92% of the patients with MS, and in three CSF specimens from one patient with DNO during the first 6 months after disease onset. The bands disappeared in two subsequent samples. This finding has never been described in MS. One patient with DNO had an apparent chronic-relapsing course probably due to steroid dependence. The clinical and CSF features of our cases favour the nosographic independence of DNO and MS.