Because a destructive immune response may be important in the pathogenesis of multiple sclerosis, clinical investigators have given patients adrenocortical steroids and immunosuppressive cytotoxic drugs. The studies to date are suggestive of a palliative effect but they have been poorly controlled or too short. We have carried out an open preliminary trial of methylprednisolone and azathioprine in twelve patients. All patients have improved and the side effects of the drugs appear manageable. We propose to perform a double-blind placebo-controlled comparative drug trial to determine the effects, if any, upon the course of MS of a combination drug regimen. The "active drug" is the combination of high dose "pulse" methylprednisolone, alternate day oral methylprednisolone for 9 months and daily azathioprine for three years. Each active drug will have a comparable placebo. An Illness Severity Score, Kurtzke's scoring method, a standard neurologic examination, and a quantitative neurologic examination will be used to detect exacerbations and progression. Peripheral blood and spinal fluid lymphocyte populations and functions, spinal fluid oligoclonal patterns, and spinal fluid myelin basic protein levels will be monitored. In a trial of 52 frequently exacerbating patients, 26 will receive the steroids and azathioprine; 26 will receive the placebos. Exacerbation rates will be compared. In another 52 progressive patients, 26 will receive the active combination; 26 will take the placebos. Progression rates will be compared.