Serum and cerebrospinal fluid (CSF) soluble Intercellular adhesion molecule-1 (ICAM-1) levels were evaluated (ELISA) in 22 untreated and 13 corticosteroid-treated active relapsing remitting (RR) Multiple Sclerosis (MS), in 10 untreated and 10 corticosteroid-treated Guillain-Barré syndrome (GBS) and in 17 non-inflammatory neurological diseases (NIND). Twenty-eight clinically inactive RR MS were assayed for serum sICAM-1 before and after 3 months treatment of 8 MIU rIFNb-1b taken s.c. every other day. High sICAM-1 serum levels above the NIND values were found in untreated clinically active MS and in untreated GBS (P50.05) but not in the untreated clinically inactive MS group. The active MS group showed significantly (P=0.0001) higher sICAM-1 serum levels if compared to the inactive group. Corticosteroid-treated active MS and GBS patients showed lower (P50.05) serum sICAM-1 levels than the corresponding untreated groups. Serum sICAM-1 levels after 3 months of rIFNb-1b treatment (P50.0001, paired t-test) resulted increased compared to pretreatment values in MS. The mean values of CSF/serum sICAM-1: CSF/serum Albumin ratios (sICAM-1 Index) in active untreated MS patients were higher compared to NIND (P50.005) and to corticosteroid-treated MS group (P=0.01). sICAM Index values in GBS did not differ from those in NIND. The results seem to suggest potential roles for serum sICAM-1 in downregulating the ongoing inflammatory response at the blood-brain barrier level and for CSF sICAM-1 in the maintenance of a central nervous system local immune response.