Many hematologic studies have shown that the erythrocyte count decreases while the size of the individual cell increases in the aged. This study was performed in order to (1) evaluate changes in the blood erythrocyte level and mean erythrocyte size in the elderly and (2) evaluate use of the deoxyuridine (dU) supression test to determine whether deficiency of vitamin B12 or folate plays any role in age-related changes of hematopoiesis. Selected for study were 102 healthy men whose ages ranged from 20 to 79 years. The erythrocyte count and hemoglobin level decreased significantly, whereas the mean corpuscular volume and mean corpuscular hemoglobin increased after 70 years of age. Fresh bone-marrow cells were obtained from 10 young (20-38 yr) and 10 aged (70-82 yr) men. Wickramasinghe's dU suppression test was modified by application of an automatic cell harvester. The results were normal in both groups. Thus, the route of dU to dTMP in a DNA synthetic pathway appeared intact, and there was no evidence of B12 or folate deficiency in the aged to explain the observed macrocytosis. However, 3H-thymidine uptake by nucleated bone-marrow cells was significantly decreased, and the ratio of 3H-uridine to 3H-thymidine uptake was greater in the old group than in the young group. These results could be explained by altered nucleic acid metabolism (unbalanced cell growth) or by a change in the proportion of the different fractions of nucleated cells.