We measured pretreatment serum levels of tumour necrosis factor-?(TNF-?) and interleukin-1?(IL-1?) in 25 patients with myelodysplastic syndrome receiving recombinant human erythropoietin (rhEPO) at dosages up to 300 Ukg thrice weekly for 12 weeks. Both TNF-?and IL-1?levels were measured using commercially available enzyme-linked immunoassays. A complete response (CR) was defined as a rise in untransfused haemoglobin concentrations of at least 2 gdl or a 100 decrease in RBC transfusion requirements over the treatment period; a partial response (PR) was an increase in untransfused haemoglobin values of 1-2 gdl or a decrease in RBC transfusion requirements equal to or greater than 50; no response (NR) was defined as a response less than a PR. After 12 weeks of rhEPO treatment, four patients showed a CR, five patients a PR, and 16 patients NR. Serum levels of both TNF-?(80.5 ± 64.8 vs 8.1 ± 4.2 ngl, P< 0.001) and IL-1?(60.4 ± 49.9 vs 8.9 ± 4.7 ngl, P< 0.001) were higher in MDS patients than in a group of 28 normal controls. Responders (CR PR) showed significantly lower serum levels of TNF-?than non-responders (21.6 ± 26.2 vs 106.3 ± 60.8 ngl, P < 0.001), whereas IL-1?concentrations between those who benefited from therapy and unresponsive cases were not significantly different (39.8 ± 48.9 vs 73.4 ± 48.2 ngl, P 0.120). It is noteworthy that TNF-?levels were within the normal range in all responsive patients but one, whereas all non-responders presented elevated cytokine concentrations. No relationship was found between TNF-?or IL-1?values and haemoglobin levels, transfusion requirement, serum EPO or ferritin concentrations. We conclude that pre-treatment TNF-?levels might help to select those MDS patients who are most likely to benefit from rhEPO treatment.