A group of 76 polycythemia vera patients was followed prospectively with bone marrow examinations at regular intervals. Six terminated in acute leukemia, preceded by an indolent preleukemic phase succeeded by a very fulminant leukemia. At autopsy, all patients had extramedullary hematopoiesis. In one of them, only the bone marrow was leukemic, suggesting that it was the primary site of this transformation. In three with leukemic involvement of nonhematopoietic organs, the infiltrate consisted of myelo- or myelomonoblasts and normoblasts. The preleukemic phase was characterized by a rapidly evolving spontaneous pancytopenia, with a drop from polycythemic blood counts within 2 mo. In the bone marrow, megaloblastoid erythropoiesis with ring sideroblasts was prominent. A similar preleukemic phase evolving in other potentially leukemic conditions, has been described. Therefore, in patients at risk, the appearance of ring sideroblasts may be regarded as an early indicator of imminent acute leukemic transformation.