After incubation of sickle anaemia (SS) erythrocytes for 1 hour at room temperature with Vinblastine (VBL) doses (0.2 mM) far lower than those capable of causing spherostomatocytosis of normal red blood cells (0.6 mM), the percent of erythrocytes which underwent swelling resulted to be overlapping the percentage of cells which showed irreversible sickling (IS) after adequate deoxygenation. Thus VBL can reveal in the SS erythrocytes the most liable cohort of cells that show IS; this may be accounted for by the fact that in both irreversibly sickled and VBL-incubated erythrocytes there are overlapping disorders of the membrane cationic traffic. The increase of the drug concentrations induced an exponentially related cohort of SS erythrocytes to swell. The observed failure of SS erythrocytes previously incubated with VBL to sickle after adequate deoxygenation is accounted for by the close interaction of the drug with the red cell membrane subunits, which renders the red cell surface unliable to undergo further morphological alterations.