A new alpha chain variant, alpha 110(G17)Ala----Thr, was detected because of subunit dissociation during the determination of the Hb A1c by automated cation exchange high performance liquid chromatography. The abnormal hemoglobin overlapped the cathodic edge of the band of Hb A in isoelectrofocusing. It was slightly unstable in the isopropanol test and had a slightly increased oxygen affinity. The abnormal alpha chain eluted slightly faster than the normal alpha chain in reversed phase high performance liquid chromatography. The amino acid substitution was determined by purification of S-alkylated alpha T-12,13 tryptic peptide, chymotryptic digestion, and sequencing of an octapeptide alpha 110-117. The abnormal alpha chain comprised about 14% of the total alpha chain. A biosynthetic study did not suggest selective loss of the abnormal chain in reticulocytes.