Interleukin-6 (IL-6) has recently been implicated in multiple sclerosis (MS), since IL-6 deficient mice were resistant to a demyelinating form of experimental autoimmune encephalomyelitis and IL-6 expression was upregulated in MS. The cytokine IL-6 and its action mediating soluble receptors (sIL-6R and sgp130) were measured in cerebrospinal fluid (CSF) and serum of 61 MS patients and 39 controls. In the presence of unchanged IL-6 concentrations, sIL-6R and sgp130 serum levels were significantly increased in MS and correlated with disease severity. Furthermore, sgp130 CSF levels were decreased in MS, suggesting a possibly altered IL-6 regulation in the CSF.