A comparison of the effectiveness of methylprednisolone sodium succinate and cyclophosphamide in the short-term treatment of experimental allergic encephalomyelitis has been made in the rabbit. Both drugs proved to be effective. At a dosage of 5 mg/kg/day cyclophosphamide did not alter the clinical course of the disease but did significantly reduce the severity of the histological changes. At 20 mg/kg/day, it had a beneficial effect on both features of the disease. Methylprednisolone appeared to act more rapidly than cyclophosphamide. Side effects of either drug were minimal. Long-term treatment of the disease, judged on the clinical course alone, was achieved for periods of three to four weeks with an intermittent regimen of methylprednisolone administration without serious side effects.