The metabolism of transferrin-bound indium and iron were compared by in vivo studies in the rat. Rats were injected with serum transferrin labeled with 111In and 59Fe, and, at intervals ranging from 20 min to 5 days after injection, they were killed. They were perfused through the portal vein with 200 ml of 0.9% saline, and the residual radioactivity, expressed as a percentage of the injected dose, was measured in liver, spleen, kidney, muscle, washed red cells, red marrow, and femur. At 5 days, 76% of the injected 59Fe was recovered in the red cell mass; only 1%-2% of 111In could then be recovered. Uptake and release of the 111In label by the femur was markedly less than that of the 59Fe. Whereas 85% of the injected 59Fe could be recovered from the circulating red cells, liver, and spleen, only about 15% of the injected 111In could be so recovered. Approximately 35% of the injected 111In was excreted, and 43% was recoverable from the carcass. The subcellular distribution of the two isotopes in the liver at timed intervals following intravenous injection was studied. While 35% of the 59Fe activity in the homogenate was associated with ferritin, only 4% of the 111In could be so identified. The results indicate a significant difference between the metabolism of 111In and 59Fe in the rat and make it unlikely that the metabolism of In in man bears much similarity to that of iron.