1. Compounds which are believed to cause derangement of the structural components of the plasma membrane and of microtubular function were preincubated with reticulocytes to study their effects on transferrin and iron uptake by the stroma and cytosol fractions of the cell. 2. Proteolytic enzymes, chelating agents (EDTA, EGTA), neuraminidase, concanavalin A and primaquine all inhibited iron binding in the cytosol fraction. Thus, their mode of action may be on the cell membrane, probably resulting in a loss of transferrin receptors or a reduced ability for the protein to interact with the receptor. 3. Pharmacologic agents known to interfere with endocytotic activity of the cell produced both inhibitory and stimulating effects on iron building by the cell. Nicotine reduced iron binding in the stroma and cytosol while colchicine and hydrocortisone enhanced cytosol-bound iron. 4. The inhibitory action of metabolic inhibitors on iron uptake by reticulocytes was accompanied by an accumulation of transferrin and ion in the stroma suggesting that a block in the iron release from transferrin occurs at the stroma level. As the stroma included some mitochondria, the possibility that such blockage may occur in these organelles cannot be ruled out entirely.