A heat-stable polypeptide from rabbit reticulocytes has been previously shown to be required for ATP-dependent protein breakdown (Ciechanover, A., Hod, Y., and Hershko, A. (1978) Biochem. Biophys. Res Commun. 81, 1100-1105) and to form covalent conjugates with proteins in an ATP-requiring reaction (Ciechanover, A., Heller, H., Elias, S., Haas, A.L., and Hershko, A. (1980) Proc. Natl. Acad. Sci. U.S.A. 77, 1365-1368). We now describe its purification, characterization, and tissue distribution. Its presence in erythrocytes at high level makes this a possible preferred source in the future.