A severely unstable hemoglobin variant, Hb Hakkari or alpha 2 beta 2 31 (B13)Leu-->Arg, has been observed in a 5-year-old Turkish girl with a severe hemolytic anemia without Heinz body formation. A modest increase in liver and spleen size was present and the level of Hb F was a high 33%. The variant could not be observed in red cells and was only detected through sequencing of the amplified beta-globin gene and also by hybridization with specific oligonucleotide probes. The parents were normal, and it is assumed that the variant occurred as a de novo mutation. Smears from bone marrow aspirates showed numerous inclusion bodies in the erythroblast and, as a result, a erythroid hyperplasia. It is suggested that the hemoglobin variant which is unstable and is readily losing its heme group because one of the heme binding sites has been lost, precipitates in the erythroblasts, thus interfering with the maturation process and causing the severe anemia.