To evaluate its clinical efficacy as well as its biologic safety, human recombinant Erythropoietin (rh-Epo) was given to 19 patients with myelodysplastic syndromes (MDS) in an open non-randomized study. Among the seventeen evaluable patients only two showed an apparent hematologic response to rh-Epo treatment. In these patients hemoglobin levels increased from a mean pretreatment value of 8.5 and 8.4 g/dl up to 11.7 and 11.3 g/dl respectively and remained relatively stable for several weeks. In one of these patients the transfusion requirement decreased from 4 to 1.5 units per month whereas the other had no transfusion requirement during the whole period of rh-Epo treatment. Interestingly, when the responding patients, after a "wash-out" period of at least ten weeks, received an additional course of rh-Epo results were less impressive. Before treatment the serum level of endogenous Epo was 18 and 110 mU/ml in the two responding patients, whereas a mean value of 532 mU/ml (range 17-2797 mU/ml) was observed in non responders. The treatment of MDS patients with rh-Epo was clinically well tolerated since no relevant side effects were registered. Moreover, no evidence of harmful cytogenetic changes nor activation of myeloid growth factor genes, as determined by Northern blot analysis of GM-CSF and G-CSF gene expression, could be related to rh-Epo treatment. Overall, it appears that administration of rh-Epo is well tolerated but the therapeutic effects appear to be restricted to a minority of patients and a limited period of time.