In this article, we have reviewed evidence to indicate that hemoglobin denaturation can cause sufficient membrane damage to contribute to red cell destruction. We have attempted to explain how hemoglobin denaturation may affect red cell membrane properties at the molecular level. Current information is consistent with the possibility that hemin, in addition to Heinz bodies, is an important factor contributing to red cell membrane damage following hemoglobin denaturation. The initial step in hemin-induced membrane damage appears to involve the oxidation of membrane protein sulfhydryl groups as well as lipids. Structural and functional membrane properties are likely to be altered. Further studies on the role of hemin in the process of red cell aging and in the pathophysiology of red cell disorders characterized by hemoglobin oxidation should yield new information regarding the role of hemin in these conditions.