Devic's disease, which is characterized by attacks of optic neuritis and myelitis (often severe and associated with limited recovery), represents a major therapeutic challenge. We report our clinical observations of eight Devic's disease patients who were treated with prednisone and methotrexate or with cyclophosphamide alone. Four patients were stabilized with methotrexate and prednisone. Of the four patients treated with intravenous cyclophosphamide, only one was stabilized. Three patients who failed cyclophosphamide were subsequently stabilized on methotrexate and prednisone. Further investigations, such as multicenter controlled trials of methotrexate and prednisone in Devic's disease, would strengthen the conclusions from this small series.