We have studied a few members of two Turkish families, who had aβ-thalassemia of the intermediate type. An abnormal hemoglobin was found in both families, which when present in association withβ°-thalassemia was considered to be the primary cause for the increased severity of the disease. In the first family this variant was Hb Knossos [β27(B9)Ala→-Ser] which occurred together with the frameshift in codon #8 type ofβ°-thalassemia. This compound heterozygosity, observed for the first time in the Turkish population was characterized by a considerable increase in Hb F production, mainly of theGγtype, as expected for a chromosome with haplotype IV. In the second family, the variant was Hb City of Hope [β69(E13)Gly→Ser] which was present in combination with an unknown type ofβ-thalassemia. The increase in Hb F production in the compound heterozygote was minimal. Reversed phase high performance liquid chromatography and the DNA amplification-synthetic oligonucleotide probe procedure were major tools in identifying the different abnormalities.