We measured sICAM-1 in paired samples of serum and cerebrospinal fluid (CSF) from patients with an attack of multiple sclerosis (MS) (n = 50) and patients with acute monosymptomatic optic neuritis (ON) as a possible first attack of MS were also included (n = 25). Based on calculations of extended indices we found evidence of intrathecal synthesis of sICAM-1 both in patients with clinically definite MS and in patients with idiopathic ON compared to neurological control subjects. The amount of intrathecally synthesized sICAM-1 correlated significantly to the CSF leukocyte count and to the concentration of myelin basic protein in the CSF. The serum concentrations of sICAM-1 were not increased in patients with demyelinating disease compared to the neurological control subjects.