SummarySeventy children homozygous for Hb S (SS) and their 111 heterozygous (AS) parents were evaluated through their erythrocytic indices, hemoglobin composition, and occasionally throughin vitroHb chain synthesis values.Three groups of SS patients and of AS parents were identified based on differences in degree of microcytosis (MCV) and (degree of hypochromia (MCH) values. The level of Hb S in the Hb S heterozygotes showed a trimodal distribution. Five SS patients had an &agr;‐thalassemia homozygosity (&agr;0&agr;/&agr;0&agr;; &bgr;S/&bgr;S) which was characterized by a distinct microcytosis and hypochromia (MCV, ≤ 70 fl; MCH, ≤22 pg). Nine SS patients had an &agr;‐thalassemia heterozygosity (&agr;0/&agr;/&agr;&agr;; &bgr;S/&bgr;S) with an MCV value of 71 to 78 fl, and an MCH value of 21.3 to 26.5 pg. Four AS parents had an &agr;‐thalassemia‐2 homozygosity with values of MCV ≤ 71 fl and MCH ≤ 23.5. The level of Hb S was < 31%. Thirty‐nine AS parents had an &agr;‐thalassemia‐2 heterozygosity characterized by an MCV value of 72 to 79 fl, an MCH value of 23.6 to 26.5, and a level of Hb S ranging between 31.0 and 36.8%.The Hb A2level in SS patients was significantly correlated with the RBC counts and the MCV and MCH (r= 0.38, −0.52, and −0.47, respectively). Significant correlations in AS parents were also noted between the MCV, MCH, RBC, and Hb S percentages (r= 0.62, 0.68, and −0.49, respectively).Although the data are limited, the simultaneous occurrence of an &agr;‐thal‐2 homozygosity seems to decrease the level of Hb F in sickle cell anemia. The presence of an &agr;‐thal‐2 heterozygosity or homozygosity together with an SS or AS condition resulted in identifiable hematologic phenotypes.SpeculationThe occurrence of microcytosis and hypochromia among SS patients in association with increased erythrocyte counts and Hb A2percentages indicates the concomitant presence of &agr;‐thalassemia‐provided &bgr; chain deficiencies have been excluded through biosynthetic experiments or through family studies. The &agr;‐thal‐2 heterozygosity (&agr;0&agr;/&agr;&agr;; &bgr;S/&bgr;S), which is associated with a mild &agr; chain deficiency, results in a slight decrease of the degree of microcytosis and hypochromia values. On the other hand, the &agr;‐thal‐2 homozygosity (&agr;0&agr;/&agr;0&agr;; &bgr;S/&bgr;S) and perhaps also the &agr;‐thal‐1 heterozygosity (&agr;0&agr;0/&agr;&agr;; &bgr;S/&bgr;S), which are associated with a moderate &agr; chain deficiency, result in a distinct microcytosis and hypochromia. The high incidence of &agr;‐thal‐2 among Black Americans requires careful consideration and may be more prevalent than an iron deficiency anemia in children with the SS and AS conditions.