1. The intra-erythrocytic concentrations of sodium and potassium and the water content have been determined for haemoglobin (Hb) SS cells and negroid Hb AA cells.
2. The erythrocyte concentration of sodium was 40% higher and potassium 10% lower in the Hb SS than in the Hb AA cells. The cell water expressed as % weight of cell (corrected for trapped plasma) was identical for both cell types.
3. Normal Caucasian erythrocytes with Hb AA contained 40–50% less sodium but about the same potassium concentration as negroid Hb AA cells.
4. Potassium efflux into buffered iso-osmotic sucrose medium was much faster in Hb SS than in negroid Hb AA cells; ouabain-sensitive active sodium transport was twice as fast in the sickle-cell erythrocytes. Passive sodium efflux of erythrocytes suspended in a physiological medium was similarly faster in Hb SS cells.
5. Under the conditions of the experiments not less than 85% of the Hb SS erythrocytes appeared biconcave. Electron-microscopic examination of ultra-thin sections of Hb SS cells revealed marked discontinuities in the membrane. This suggests definite membrane alterations, which have probably resulted from the sickling-unsickling cycles occurring during the life-span of the cells.
6. It is suggested that the enhanced active sodium transport in the Hb SS erythrocyte is secondary to the augmented passive cation efflux, which in turn results from the leakiness of the erythrocyte membrane produced by the sickling-unsickling process.