Hypotransferrinemic (HP) mice have a splicing defect in the transferrin gene, resulting in < 1% of the normal plasma levels of transferrin. They have severe anemia, suggesting that transferrin is essential for iron uptake by erythroid cells in the bone barrow. To clarify the significance of transferrin on iron delivery to the bone marrow, iron concentration and 59Fe distribution were determined in 7-day-old HP mice. Iron concentration in the femur, bone containing the bone marrow, of HP mice was approximately twice higher than in wild type mice. Twenty-four h after injection of 59FeCl3, 59Fe concentration in the bone and bone marrow of HP mice was also twice higher than in wild type mice. The present findings indicate that iron is abnormally delivered to the bone marrow of HP mice. However, the iron seems to be unavailable for the production of hemoglobin. These results suggest that transferrin-dependent iron uptake by erythroid cells in the bone marrow is essential for the development of erythrocytes.