Several studies have reported a positive correlation between levels of soluble adhesion molecules in serum or cerebrospinal fluid and cranial MRI activity. We performed a cross-sectional study in 46 patients with newly diagnosed MS and determined levels of soluble intercellular adhesion molecule-I (sICAM-I) as well as vascular cell adhesion molecule-I (sVCAM-I) in correlation to the number and area of gadolinium enhancing lesions on cranial magnetic resonance images (MRI). The data revealed a significant positive correlation between sVCAM-I serum levels and gadolinium enhancing lesions. In addition, CSF to serum ratios for sICAM-I and sVCAM-I correlated to MRI activity. In patients with a single enhancing lesion (SEL) there was a negative correlation between the QsCAM and the distance of the SEL to the ventricles. As these adhesion molecules are stable and markers of disease activity in MS, we further investigated sVCAM-I serum levels during treatment with interferon beta-Ib (Betaferon). Significant increases in serum levels for sVCAM-I in patients receiving Betaferon were associated with a favourable treatment response after 1 year in 17 out of 19 patients and correlated to decreased MRI activity, whereas stable or reduced sVCAM-I levels occurred more often in non-responders (five out of six patients). Therefore it can be hypothesized that soluble adhesion molecules are released from cerebral endothelial cells as an early immunoregulatory activity of the immune system to reduce cellular traffic across the blood brain barrier and this is further enhanced by IFN-beta treatment.