The reported scanning (SEM), transmission (TS), and freeze-etching (FE) electron microscopic studies have agreed in confirming that in thalassaemic erythrocytes, previously incubated with brilliant cresyl blue (BCB), the unpaired alpha chains precipitate in the central portions of the cell whereas excess beta chains locate in the submembranous regions. This is due to the fact that beta chains, possessing two thiols instead of only one (as in alpha chains), are more liable to bind to similar groups contained in the inner red cell leaflet. Less soluble alpha chains tend to form inter-chain bridges and thus precipitate centrally. SEM observations have given evidence that on the surface of the affected red cells denaturated alpha chains give rise to large and shallow invaginations whereas denatured beta chains lead to diffuse wrinkled appearance. The causes of the different SEM aspects have been suggested.