We assessed the effect of intravenous high-dose methylprednisolone (IVMP) on cerebral reactivity in multiple sclerosis (MS) patients during exacerbations by means of functional transcranial Doppler imaging. Forty-eight clinically defined MS patients were evaluated with visual evoked potentials (VEP) and functional transcranial Doppler sonography (TCD) of both posterior cerebral arteries before and after 5 days of 1000 mg IVMP. After treatment, mean Expanded Disability Status Scale score, mean blood flow velocities and mean blood flow velocities at rest and at stimulation, significantly decreased (p < 0.0001, for each). The change in cerebral blood flow velocity ratio (CBFv) with visual stimulation after treatment increased slightly (p = 0.20). All TCD parameters were not significantly correlated with VEP changes. In conclusion, we observed significant changes in CBFv with a non-significant increase in vascular reactivity after treatment with IVMP in exacerbations of MS. Case-control studies are necessary to draw conclusions regarding the beneficial effects of IVMP treatment.