The development of red blood cells (erythrocytes) is distinguished by high-level production of the oxygen carrier, haemoglobin A (HbA), a heterotetramer of α- and β-haemoglobin subunits. HbA synthesis is coordinated to minimize the accumulation of free subunits that form cytotoxic precipitates^,,. Molecular chaperones that regulate globin subunit stability, folding or assembly have been proposed to exist but have never been identified. Here we identify a protein stabilizing free α-haemoglobin by using a screen for genes induced by the essential erythroid transcription factor GATA-1 (refs , ). Alpha Haemoglobin Stabilizing Protein (AHSP) is an abundant, erythroid-specific protein that forms a stable complex with free α-haemoglobin but not with β-haemoglobin or haemoglobin A (α₂β₂). Moreover, AHSP specifically protects free α-haemoglobin from precipitation in solution and in live cells. AHSP-gene-ablated mice exhibit reticulocytosis and abnormal erythrocyte morphology with intracellular inclusion bodies that stain positively for denatured haemoglobins. Hence, AHSP is required for normal erythropoiesis, probably acting to block the deleterious effects of free α-haemoglobin precipitation. Accordingly, AHSP gene dosage is predicted to modulate pathological states of α-haemoglobin excess, such as β-thalassaemia.