The aim of this study was to evaluate soluble proteins of tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and IL-6 receptor subunit gp80 (sIL-6R gp80), as markers of multiple sclerosis (MS). Paired cerebrospinal fluid (CSF) and serum samples of 20 MS patients and 15 controls suffering from non-inflammatory neurological diseases have been assayed retrospectively using monoclonal antibodies-based ELISAs. While TNF-alpha could not be detected in CSF, it was measurable in 20% of total sera. Interleukin-6 was measurable in 5% of total CSF and in 10% of total sera only. However, soluble IL-6R gp80 protein subunit was readily measurable, showing sera concentration (pg/mL) about 34 times higher and specific content (pg/mg total protein) around five times lower than those in paired CSF, similarly for both group of patients. No significant difference of sIL-6R gp80 level, which could be disease-, gender- or age-related, and no correlation of CSF sIL-6R gp80 content with that of paired serum or with routine clinical data for CSF, have been observed. We have concluded that soluble proteins of TNF-alpha, IL-6 and sIL-6R gp80 assayed by monoclonal antibodies-based ELISAs could not serve as markers of the MS activity.