Hb Adana [HBA2: c179G>A ( or HBA1); p. Gly60Asp] is a rare hemoglobin ( Hb) variant due to a mutation at codon 59 of the alpha 2- or alpha 1-globin gene resulting in a glycine to aspartic acid substitution. Two siblings with a unique coinheritance of Hb Adana and Hb Constant Spring (Hb CS, alpha 142, Term -> Gln, TAA>CAA; HBA2: c.427 T>C) (alpha(codon) (59)alpha/alpha(CS)alpha), were compared phenotypically with another two siblings carrying the Hb Adana mutation and a 3.7 kb deletion (alpha(codon) (59)alpha/-alpha(3.7)). Although they all had alpha-thalassemia intermedia ( alpha-TI), the former were clinically more severe than the latter. The first pair of siblings presented at a much younger age than the second pair and showed lower Hb levels and significant extramedullay hemopoiesis. Another case of a hydropic fetus as a result of Hb H/Hb Adana is also described. Their clinical phenotypes and hematological parameters are all presented for comparison.