Although most children with acute lymphoblastic leukemia (ALL) are anemic at the time of diagnosis, the cause of this anemia remains obscure. In an effort to characterize the anemia, we analyzed the mean corpuscular volume (MCV) at the time of diagnosis. The MCV was selected because of the observation that older erythrocytes have a reduced MCV and an anemia presumably related to decreased red blood cell production should be reflected by a reduced MCV. A total of 54 patients fulfilled the criteria for analysis. Of this group, 33 per cent had an increased MCV, 61 per cent had a normal MCV, and 6 per cent had a decreased MCV for age. Patients with an increased MCV were found to have a significantly lower hemoglobin and platelet count. The number of females in the group with the increased MCV was 83 per cent as contrasted with 43 per cent in the group with a normal MCV. At relapse, 71 per cent of patients with an initially increased MCV had an elevated MCV as contrasted with only 23 per cent in the group with an initially normal MCV. These observations suggest that in patients with ALL and an increased MCV, a maturation defect may be present that affects all cell lines and may be the result of a diffusible substance released from the leukemic cells. The MCV cannot be used as a reflection of mean cell age in patients with ALL and does not support the belief that the anemia in ALL is merely the result of a "crowding-out" process.