A 25-yr-old Indian (Asiatic) woman investigated for a life-long anemia was found to have a hitherto undescribed structural hemoglobin variant α2Aβ222-glu→gln, which was found independently and designated Hb D Iran by Rahbar in members of a family from Iran. In the present case, Hb D Iran was found in association with high A2 thalassemia. The replacement of glutamic acid by glutamine at β 22 (helical residue B4) was demonstrated by thin-layer chromatography after automated Edman sequencing. This is the fourth substitution to be described at β 22; the previous substitutions were (1) G Coushatta (ala); (2) E Saskatoon (lys); (3) G Taipei (gly). Helical residue B4 is an external residue, does not participate in α-β or protein-heme contacts and hemoglobin D Iran resembles Hb A in visible spectra, O2 equilibria in dilute solutions and heat stability. Since the propositus and her mother who was also heterozygous for β thalassemia had similar degrees of anemia, no interaction between this variant and β thalassemia was evident. The presence of this Hb variant in Iranians and in Western Indians may reflect the migrations of populations in these areas centuries ago.