The increasing interest in the use of Tc-99m-labeled red blood cells encourages exploration into the site and mechanism of binding of Tc-99m to the RBC components. The components isolated from the labeled red cells were the lipid and protein of the membrane, heme, and the alpha and beta chains of the globin. The binding occurs mainly to the protein moiety, and preferentially to the beta chain of the globin, where the specific activity was found to be 28 +/- 6 times that of the alpha chain. The mechanism of binding is discussed. The role of heme in the binding is not clear.