Recently it has been shown that axonal damage occurs in all stages of multiple sclerosis (MS) and can be detected very early in the course of the disease. Axonal pathology has been related to the inflammatory demyelinating environment, but its dependence on inflammation is still unknown. We measured tau protein and 14-3-3, two intracellular proteins expressed in neurons and glial cells, in the cerebrospinal fluid (CSF) of 114 patients with MS, in 79 patients with other inflammatory neurological diseases (IND) and in the CSF of 60 patients with non-inflammatory neurological diseases (NIND) as controls. Concentrations of tau protein and 14-3-3 were measured by enzymelinked immunoassay and were correlated to the following immune parameters in the CSF: leukocyte cell count, total protein, albumin CSF/serum ratio as a marker of disruption of the blood-brain barrier, immunoglobulin (IgG concentrations and IgG index as an indicator for intrathecal synthesis of IgG in the CSF). Both in MS and IND tau protein levels were significantly higher than in NIND (p<0.05). In MS patients levels of tau protein were positively correlated with the IgG index (p<0.05) and this association was present in both relapsing remitting MS (RRMS) (p<0.05) and progressive MS (p<0.05). Tau and 14-3-3 were also correlated with the IgG index in patients with IND (p<0.05). These findings strengthen the hypothesis that inflammation may be at least in part responsible for the axonal damage observed in MS patients.