AbstractRed cell morphology was studied after the induction of echinocytic transformation by metabolic depletion, Ca2+loading, and salicylate and stomatocytic transformation with chlorpromazine. The results indicate that the red cell has an energy‐dependent shape control mechanism that allows it to counteract shape‐changing stimuli such as metabolic depletion. Albumin was found to induce stomatocytic transformation, whereas γ‐globulins induced echinocytic transformation. Loading of the red cell with calcium resulted in polymorphous membrane damages such as submembranous, “blister‐like” lesions, and membrane disintegration; the red cell age had no influence on this process. Conversely, the stomatocyte‐echinocyte transformation induced by chlorpromazine and salicylate was shifted towards echinocytes in density‐separated old red cells. Sphero‐stomatocytes were capable of echinocytic transformation with spicule formation within the red cell vacuoles, whereas sphero‐echinocytes were unable to undergo stomatocytic transformation without hemolysis. These observations may help to unravel the complexity of echinocyte‐stomatocyte transformat