Using amplification, allele-specific oligonucleotide (ASO) hybridization and DNA sequencing we have documented the molecular basis of 64 α- and 123 β-thalassemia (thai) chromosomes, and the haplotypes of 18 βs chromosomes from patients followed in three hospitals in Kuwait. Of the 30 chromosomes from 15 patients with Hb H disease, 26 (86.7%) carried the polyadenylation (poly A) signal mutation (AATAAA→AATAAG) in the α2-globin gene, 3 (10%) had the -α (3.7 kb) deletion, and 1 (3.3%) had the pentanucleotide deletion in the 5´ IVS-I splice junction (α-5ntα). As many as 12 different β-thal mutations were identified; 6 Mediterranean alleles [IVS-II-1 (G→A), IVS-I-6 (T→C), codon (CD) 39 (C→T), IVS-I-110 (G→A), CD 8 (-AA), and IVS-I-1 (G→A)] were present in 79 (64.2%) of the chromosomes tested. Four East Indian alleles [IVS-I-5 (G→C), IVS-I 3´ end -25 nt deletion, CDs 8/9 (+G), and 619-bp deletion] were found in 31 (25%), and the two Kurdish/Iranian alleles [CD 44 (-C) and CDs 36/37 (-T)] were found in 13 (10.6%) chromosomes. Fourteen βs chromosomes carried haplotype No. 31 (Saudi Arabia/ India); 3 had haplotype No. 19 (Benin), and 1 was a hybrid with haplotype No. 31-specific characteristics in the locus control region hypersensitive site-2 (LCR-HS-2), and haplotype No. 19-specific mutations in the 5´ flanking region of the Gγ-promoter. The patient homozygous for haplotype No. 19 was a Jordanian, while the others were Kuwaiti Arabs. The latter appear to be fairly homogeneous in terms of the prevalent α-thal determinants and βs-haplotypes, but there is considerable heterogeneity of their β-thal alleles. This has implications for genetic counseling and prenatal diagnosis programs.