Dihydrofolate reductase (FH2-R) was studied cytochemically in the bone marrow erythroblasts of 20 normal controls and 46 patients with myelodysplastic syndromes (MDSs) classified according to FAB, prior to therapy. The reaction product was quantified for the same samples with a Vickers M86 microdensitometer. The enzyme activity progressively decreased during the normal differentiation of the erythroid cells and persisted at high levels in MDS cells. The high level of FH2-R may be related to the malignant transformation of the cells, or to increased compensatory erythropoietic activity of ineffective erythropoiesis, or to both.