Interleukin- 15 (IL- 15) is a novel proinflammatory cytokine having similar biological activities to IL- 2 which is implicated in the pathogenesis of multiple sclerosis. It is produced by activated blood monocytes, macrophages and glial cells. There is little information about the involvement of IL- 15 in the development of multiple sclerosis (MS). The objective of our study was to measure IL- 15 serum and cerebrospinal fluid (CSF)levels in MS patients and to correlate serum and CSF IL- 15 concentrations with clinical parameters of the disease. CSF IL- 15/Serum IL- 15 ratio (c/s IL- 15 ratio) was introduced to assess the origin of elevated IL- 15 levels. Materials and methods: We measured serum and CSF IL- 15 levels in 52 patients with MS and 36 age and gender matched patients with inflammatory (IND) and noninflammatory neurological diseases (NIND) studied as control groups. IL- 15 levels were correlated with clinical parameters as duration, disability, MRI activity and clinical subtypes of the disease. Results: MS patients were found to have significantly higher serum IL- 15 levels compared with IND (p = 0.00016) and NIND patients (p = 0.00045). Elevated levels of IL- 15 were also found in CSF samples from MS patients compared with patients with IND (p = 0.00034) and NIND (p = 0.0003). Among MS subgroups there were no statistically different IL- 15 serum and CSF concentrations. No significant correlation of serum and CSF IL- 15 concentrations with MRI activity, disability assessed by EDSS score and duration of the disease were also found. C/S IL- 15 ratio was found lower in MS patients compared with IND (p=0.01) and not significantly different compared with NIND patients (p = 0.14) suggesting that systemic activation might be the source of high CSF IL- 15 levels in MS patients. Conclusions: Our findings suggest a possible role of IL- 15 in the immunopathogenetic mechanisms of MS. It is produced by activated monocytes, macrophages and glial cells. There is little information about the involvement of IL-15 in the development of multiple sclerosis (MS). The objective of our study was to measure IL-15 serum and cerebrospinal fluid (CSF) levels in MS patients and to correlate serum and CSF IL-15 concentrations with clinical parameters of the disease. CSF IL-15 / Serum IL-15 ratio (c / s IL-15 ratio) was introduced to assess the origin of elevated IL- 15 levels. Materials and methods: We measured serum and CSF IL- 15 levels in 52 patients with MS and 36 age and gender matched patients with inflammatory (IND) and noninflammatory neurological diseases (NIND) studied as control groups. IL-15 levels were correlated with clinical parameters as duration, disability, MRI activity and clinical subtyp es of the disease. Results: MS patients were found to have significantly higher serum IL-15 levels compared with IND (p = 0.00016) and NIND patients (p = 0.00045). Elevated levels of IL-15 were also found in CSF samples from MS patients compared with patients with IND (p = 0.00034) and NIND (p = 0.0003). No significant correlation of serum and CSF IL-15 concentrations with MRI activity , disability assessed by EDSS score and duration of the disease were also found. C / S IL-15 ratio was found lower in MS patients compared with IND (p = 0.01) and not significantly different compared with NIND patients (p = 0.14) suggesting that systemic activation might be the source of high CSF IL-15 levels in MS patients. Conclusions: Our findings suggest a possible role of IL-15 in the immunopathogenesis mechanisms of MS.