This is a revised proposal that aims to examine the mechanisms by which iron is taken up into cells from transferrin. Very little is known about this important aspect of iron metabolism. The Applicant will use rabbit reticulocytes as a model system, but his findings should be generally applicable to transferrin mediated iron uptake in all cells. In addition, he will examine the mechanism responsible for defective iron uptake into the erythroid cells of the Belgrade rat. This animal carries a spontaneous recessive mutation that impairs iron uptake into cells, leading to iron-deficient erythropoiesis. The investigator has greatly sharpened the focus of the proposal and has built a logical sequence of experiments. The Investigator has also provided new preliminary data that strengthen several of the hypotheses that he plans to test.