We performed a prospective study to correlate quantiative brain magnetic resonance imaging activity (gadolinium-diethylenetriaminepentaacetic acid enhancement) to cerebrospinal fluid and serum levels of soluble adhesion molecules in 46 patients with newly diagnosed multiple sclerosis (MS) and 30 control subjects with other diseases of the central nervous system. In all patients, magnetic resonance imaging of the brain and lumbar puncture were performed on the same day. In 32 (70%) of 46 MS patients, 8 (80%) of 10 patients with acute viral encephalitis, but none of the control subjects with noninflammatory diseases, gadolinium-enhancing lesions were detected. There was a significant correlation between the cerebrospinal fluid/serum ratios for soluble intercellular adhesion molecule-1 and soluble vascular cell adhesion molecule-1 as well as serum levels for both molecules and the area of gadolinium-enhancing lesions. No obvious correlation was observed between magnetic resonance imaging findings and cerebrospinal fluid cell count, protein concentration, or intrathecal immunoglobulin production. In patients with a single periventricular gadolinium-enhancing lesion (n = 16), we observed a strong negative correlation between the distance from the lateral ventricles and the cerebrospinal fluid/serum ratios for soluble intercellular adhesion molecule-1/albumin and soluble vascular cell adhesion molecule-1/albumin. These results suggest that intrathecal production of the two soluble adhesion molecules, as well as serum levels for soluble vascular cell adhesion molecule-1, in patients with MS reflect magnetic resonance imaging activity of typical periventricular lesions.