The effects of long term melphalan-prednisolone (MP) therapy was studied on 12 patients with POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) syndrome. Six were treated with MP every six weeks for 16 to 52 months; three also with cyclophosphamide, and three with localised irradiation for osteoclastic lesions. Five of the six survived during the follow up period and showed various degrees of lessening of their neuropathy and other symptoms. There were no serious side effects. The other six patients received treatments that included corticosteroids, short term chemotherapy, or irradiation, but not long term chemotherapy. Five showed transient lessening of their non-neurological symptoms, and one, obvious neurological improvement. Five of these six patients died from nine to 70 months after POEMS onset. The findings suggest that long term MP therapy may be an effective treatment for the POEMS syndrome.