Summary. Laboratory observations suggest that, in some myelodysplastic syndromes (MDS), immune mechanisms may contribute to the impaired blood cell production. Tumor necrosis factor α (TNF‐α), a potent inhibitor of haematopoiesis, has been hypothesized to mediate suppressive effects in MDS: TNF‐α levels are elevated and correlated with marrow apoptosis and cytopenia. Inhibition of TNF‐α production using the soluble TNF receptor (Enbrel) has been successful in rheumatoid arthritis, and we have now applied the same principle to MDS. We determined spontaneous TNF‐α production by marrow cells in MDS; TNF‐α production was elevated (> mean + 2 × SD of controls) in > 1/3 of patients, but did not correlate with clinical parameters. Sixteen patients participated in a 3‐month pilot study of Enbrel. The drug was well tolerated and 15 patients were evaluable. Of these, one became temporarily (14 weeks) transfusion independent. In another patient, absolute neutrophil count (ANC) rose from 0·5 × 109/l to 0·84 × 109/l. Serious infections were seen in two out of six neutropenic patients. Progression to refractory anaemia with excess blasts in transformation (RAEBt) or leukaemia was observed in three patients. When the effects of Enbrel on haematopoietic colony formation were studied, no significant increase was seen in MDS and there was no correlation with TNF‐α levels. Although anti‐TNF therapy with Enbrel was well tolerated at the dosages used in MDS, its efficacy as a single agent appears low.