Transferrin, the plasma iron transport protein, has two iron-binding sites but is usually only partly saturated. (Essentially all plasma iron is bound to transferrin.) Thus, changes in transferrin saturation reflect differences in the concentrations of plasma iron and/or transferrin. Developmental changes in red cell ferritin content coincide with a 2.5 times increase in plasma transferrin and a proportional decrease in saturation, in the bullfrog model system. The possible relationship of the degree of transferrin saturation and structure on the distribution of iron between heme and ferritin was examined in suspensions of reticulocytes, which synthesize both ferritin and heme. The extra transferrin in adult plasma was indistinguishable from transferrin in tadpole plasma in terms of the ability to donate iron to red cell heme and ferritin in vitro and in terms of surface charge (pI 6.55, 6.34), molecular weight (73,000), carbohydrate content (2%), amino acid composition, and immunological reactivity. Only the saturation in vivo appeared to differ. When the saturation of transferrin was manipulated in vitro, an effect on the relative distribution of iron between heme and ferritin was observed. The heme-synthesizing system consumed a disproportionately large amount of the delivered iron until it was saturated, a point which coincided with transferrin saturation; as the degree of transferrin saturation decreases, iron delivered to red cell iron stores (ferritin) decreases disproportionately. Thus, the developmental increase in plasma transferrin and consequent decrease in saturation minimize the amount of iron available for storage in red cells. The effect is further enhanced by the decreased ability of adult erythrocytes to incorporate iron from transferrin, a property which may be related to quantitative changes observed in iodination of a Mr = 168,000 membrane protein.