THE thalassaemia syndromes are associated with unbalanced synthesis of the globin chains of haemoglobin A (α₂β₂) (refs. 1–3). In cells of patients with α thalassaemia, there is a relative deficiency of α chain production; as a consequence, β chain tetramers known as haemoglobin H are formed and can be found in considerable quantities in the cells of these patients⁴. In the cells of patients with β thalassaemia, there is a marked decrease in β chain synthesis^3,5,6, while α chain synthesis continues at a normal rate⁷. This leads to an accumulation of newly synthesized α chains which are not present in haemoglobins A or F, but can be characterized as α chain aggregates, ranging from monomers to tetramers, in the soluble fraction of the cell^8,9. In spite of this biosynthetic evidence for the production of large amounts of α chain aggregates in the cells of patients with thalassaemia major (the homozygous condition) and minor (the heterozygous condition), intact α chains have not been reported in the cells of patients with thalassaemia minor, and are present in only small amounts in some cases of thalassaemia major¹⁰. One explanation of this is that the cells containing the greatest number of α chains uncombined with β or γ chains are preferentially destroyed in the bone marrow, or by the spleen or liver when they reach the peripheral blood¹¹. On the other hand, the reticulocytes which survive in peripheral blood synthesize more α chains than β or γ chains^3,5,6. This suggests the alternative possibility that α chains unassociated with β or γ chains might be selectively degraded by intracellular enzymatic proteolysis. Selective proteolytic digestion of normal globin chains has not been reported to date. Our results reported here, however, indicate that α chains synthesized in the cells of patients with β thalassaemia undergo significant intracellular proteolysis, while those present in non-thalassaemic cells do not.