The activities of the metalloproteinase gelatinase B, and the presence of IL‐6, an inducer of metalloproteinase inhibitors, were investigated in CSF samples of 190 patients with multiple sclerosis (MS;n= 55), optic neuritis (ON;n= 46), other inflammatory neurological diseases (OIND;n= 27) or control patients (CON) with non‐inflammatory neurological diseases (n= 62). IL‐6, measurable as hybridoma growth factor activity (detection limit 3 pg/ml), was found in only four of these 190 CSF samples (three OIND, one CON). Elevated CSF gelatinase B levels were detected in 40%, 35% and 54% of the patients with MS, ON and OIND, respectively, while all control CSFs were devoid of gelatinase B activity. Clinical and laboratory data were compared with gelatinase B levels. No correlation was found between the CSF cytoses and gelatinase B levels, suggesting that this enzyme in the CSF originates from CNS lesions rather than from CSF cells. However, the occurrence of the gelatinase B significantly correlated with the IgG index in the MS patient group. This study stimulates further investigation into the possible usage of protease inhibition in demyelinating dis