Alpha hemoglobin stabilizing protein (AHSP) is a small protein of 102 residues induced by GATA-1, Oct-1- and EKLF. It is synthesized at a high level in the red blood cell precursors and acts as a chaperone protecting the alpha hemoglobin (AH) chains against precipitation. AHSP and AH form a heterodimer complex that exhibit monophasic CO binding kinetics, as observed for isolated Hb subunits, but with a rate three times slower, indicating with some heme pocket reorganization. In the absence of AHSP, AH oxidizes and precipitates within the erythrocyte precursors of the bone marrow leading to apoptosis and defective erythropoiesis. In vitro the binding of AHSP to AH also leads to the oxidation of AH, but the complex is more resistant to protein unfolding. AHSP could act as a modulating factor in beta-thalassemia. Recent studies showed more severe thalassemic syndromes in patients with decreased levels of AHSP and in one patient who carried a structurally abnormal AHSP. Some alpha chain variants with structural abnormality located in the contact area between AH and AHSP exhibit an instability and a thalassemic like syndrome. We suggested that there is a disturbed interaction between AH variants and AHSP. To study this interaction, we constructed the pGEX-α-AHSP vector permitting to express together human AH and AHSP. Preliminary results obtained with recombinant Groene Hart AH and Diamant AH, in which proline 119 is replaced by a serine and a leucine, respectively, showed an impaired interaction between these variant AH and AHSP.