The present studies were performed to identify reticulocyte membrane receptors for transferrin. Rat reticulocytes were labeled in vitro with l25l via lactoperoxidase; cell ghosts were then prepared and solubilized with Triton X-100. Binding of soluble membrane-125I components to transferrin conjugated to Sepharose (Seph-tfn) was three times greater than to albumin conjugated to Sepharose (Seph-alb). Soluble membrane-125I components released from Seph-tfn by 8 M urea rebound to Seph-tfn but not to Seph-alb. Polyacrylamide gel electrophoresis (PAGE) of membrane components released from Seph-tfn showed three proteins with estimated molecular weights of 76,000, 95,000, and 145,000 daltons. Antibody to transferrin formed a precipitate upon incubation with soluble reticulocyte membrane components but not with soluble membrane components from erythrocytes or reticulocytes exposed to trypsin. PAGE of precipitates formed by incubation of antitransferrin and soluble 125I-reticulocyte membrane components showed three nonantibody proteins and corresponding 125l peaks with molecular weights of 76,000, 95,000, and 145,000 daltons. All three proteins increased in quantity when the amount of transferrin was increased in the immune precipitate by addition of “cold” exogenous transferrin, but only the 95,000- and 145,000-dalton components had increased 125l. These data indicate that two reticulocyte membrane components (95,000 and 145,000 daltons) can be iodinated and shown to have affinity for transferrin (76,000 daltons). The lack of components with such properties in membranes from erythrocytes or trypsinized reticulocytes, cells lacking the ability to bind transferrin, suggests that the two reticulocyte membrane proteins function as the transferrin receptor.