The shapes of acanthocytic erythrocytes have been thought to be related to changes of the organization of the membrane components. In this study, acanthocytes from a patient with chorea-acanthocytosis and a patient with McLeod syndrome were examined. These acanthocytes had a greater tendency to form spikes than normal erythrocytes in an incubation culture system, indicating their weakness against membrane tension. The membrane skeletons of erythrocytes from both patients were examined by our erythrocyte-splitting method followed by the quick-freezing and deep-etching method. The ultrastructural organization of the membrane skeletons was heterogeneous even in individual erythrocytes, indicating regional changes in the compactness of their meshworks. In the process of erythrocyte splitting, some erythrocyte membranes became reversed and protruded into the cytoplasmic side. In these regions, there were fewer filamentous structures. The focal membrane skeletal changes, which are probably one of the factors that induce the phenotype of an acanthocytic erythrocyte, were demonstrated for the first time by this method.