We studied tumor necrosis factor-alpha (TNF-alpha) levels in serial serum samples from 3 consecutive patients who had a complete form of POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes) syndrome and early weight loss. Serum TNF-alpha levels were compared with those of 10 patients with multiple myeloma (5) or Waldenström's macroglobulinemia (5). Elevated serum levels of TNF-alpha were found in the patients with POEMS syndrome (two- to eightfold increase in 10 of 11 samples) and not in those with other malignant plasma cell dyscrasias. These results are in keeping with the hypothesis of a role for nonimmunoglobulinic mediators in the pathogenesis of the POEMS syndrome, and are consistent with previous reports of TNF-alpha overproduction in inflammatory demyelinating neuropathies and cachectic states.