Leukemic transformation (LT) free survival was studied in 30 patients with myelodysplastic syndromes (MDS). In 15 cases, 4-6 micrograms/day of 1-hydroxyvitamin D3 was administered, for a median duration of 17 months (D-group), other subjects had no therapy (N group). LT free survival of the D group had significant advantage over that of the N group according to the Kaplan-Meier method (P less than 0.001). In addition, 7 cases in the N group developed acute leukemia, in contrast to only one in the D group (P less than 0.05). These results suggest that oral administration of 1-hydroxyvitamin D3 prevents the progression of MDS to overt leukemia under the effect of differentiation capacity from blasts to monocytes.