We performed X-linked restriction fragment length polymorphism (RFLP)-methylation analysis to study the clonality of hematopoiesis in five patients with myelodysplastic syndromes (MDS), who had responded to chemotherapy. Two patients had MDS in blast crisis, two had refractory anemia with an excess of blasts in transformation (RAEB-T), and one had acute myelogenous leukemia with trilineage myelodysplasia (AML-TMDS). Following the administration of low-dose cytarabine therapy or of conventional intensive chemotherapy, we observed a reversion to polyclonal hematopoiesis in three patients who achieved a complete remission (CR). Polyclonal hematopoiesis persisted in one patient in CR, and monoclonal hematopoiesis persisted in another patient of minor response. These results indicate that polyclonal hematopoiesis can be restored in some MDS patients who achieved CR. We are encouraged, therefore, to administer intensive consolidation chemotherapy to prolong the duration of remission.