An atypical form of macrocytosis termed volumetric macrocytosis is described. In contrast to the macrocyte associated with megaloblastic anemia and the pseudomacrocyte caused by viscoelastic defects, the volumetric macrocyte is characterized by an increased mean corpuscular volume and a normal cell diameter. The volumetric macrocyte proves to be thicker than the normocytic red blood cell. This large erythrocyte is overhydrated and contains an increased quantity of hemoglobin. The cell has many characteristics in common with the red blood cells of neonates. Volumetric macrocytosis accompanies sustained hydroxyurea therapy and may represent a drug-induced dyserythropoiesis.