The efficacy of dexamethasone (DX) and methylprednisolone (MP) at high (HD) and low (LD) dose in acute multiple sclerosis (MS) relapses was evaluated by a double-blind trial in 31 patients followed for 1 year. DX and HDMP were similarly efficacious in promoting recovery, while LDMP was ineffective in the short-term outcome and was followed by an early clinical reactivation. The different outcomes seem to be related to different immunomodulating effects, mainly on cerebrospinal fluid (CSF) IgG synthesis and on peripheral blood and CSF CD4+ lymphocyte subsets.