In this controlled study, we investigated the serum and cerebrospinal fluid (CSF) levels of soluble intercellular adhesion molecule-1 (sICAM-1) in relapsing-remitting multiple sclerosis (RRMS) patients and changes in the levels of this adhesion molecule during interferon-beta1b (IFN-beta1b) treatment. We also investigated the changes in the levels of sICAM-1 in correlation with disease activity and with findings on magnetic resonance images (MRI). The study included 24 patients (16 females and 8 males) who were confirmed to have RRMS based on the criteria of Poser et al. Sixteen of the patients received IFN-beta1b (Betaseron, Berlex Laboratories, Schering AG Germany, Berlin) treatment, and 8 did not receive this therapy. The levels of sICAM-1 in the MS patients' serum and CSF were significantly higher than levels in individuals with noninflammatory neurologic disease (p = 0.0081 and p = 0.0001, respectively). In the first 3 months of the study, MS patients treated with IFN-beta1b showed a significant rise in sICAM-1 levels (p = 0.0023), whereas their untreated counterparts showed no significant change. Neither of the groups showed a significant correlation between sICAM-1 level and disease activity demonstrated by MRI or between sICAM-1 level and clinical disease activity. The findings suggest that IFN-beta1b treatment may have a short-term upregulating effect on sICAM-1.