A phase II trial was conducted to explore the efficacy and tolerability of combining thalidomide (100 mg/d p.o.) with an erythropoietic growth factor (darbepoietin-alpha 2.25 micro g/kg/d s.c.) in patients with low-to-intermediate-risk myelodysplastic syndromes (MDS). However, the trial had to be discontinued early because of an unexpectedly high incidence of thromboembolic events. Of the first seven patients enrolled, two developed deep-vein thrombosis and one died of massive pulmonary embolism. We concluded that thalidomide might significantly increase the thromboembolic risk of erythropoietic proteins in MDS patients. Careful clinical surveillance and thrombosis prophylaxis (heparin or oral anticoagulation) should be considered for MDS patients undergoing combined treatment with thalidomide and erythropoietic growth factors.