Binding of hemoglobin chains to erythrocyte membranes is an obligatory step in the conversion of hemoglobin to acid-soluble products by erythrocyte proteinases. This binding requires limited proteolysis of the hemoglobin chains and also modification of the inner surface of the erythrocyte membrane, both of which result from the action of a soluble Ca2+-requiring neutral proteinase. Final digestion of the bound hemoglobin chains in the membrane complex results from the action of intrinsic membrane endopeptidases. Regulation of the activity of the Ca2+-requiring proteinase by the substrate provides a mechanism for the initiation of selective protein turnover.