Erythrocyte aging, accompanied by reduced deformability and low ATP level, is considered to be among the factors limiting the survival of old erythrocytes. The aim of this study was to observe the effect of reversible erythrocyte shape changes of discocyte-echinocyte-discocyte, following ATP-depletion and repletion with adenosine of normal human erythrocytes, on the cytoskeletal network. The effect becomes evident from electron microscopical observations on Triton-treated erythrocyte membranes. The two-dimensional lattice of spectrin-actin junction polygons increases in size in ATP-depleted erythrocytes. This may be due to the spectrin elasticity permitting an expansion of the skeletal lattice. The observations demonstrate alterations in the configuration of the filamentous units visualized in the cytoskeleton during the process of reversible erythrocyte shape changes, a capacity which is limited in aged human erythrocytes.