We analyzed the mutations present in 19 patients withβ-thal-assemia major, in 11 patients with Hb S-β-thalassemia, and the Bshaplotypes of 34 patients with sickle cell anemia. The study included 84 relatives. Dot-blot analysis of amplified DNA with various specific oligonucleotide probes identified 11 different knownβ-thalassemia mutations and frameshifts; a new frameshift at codons 25/26 (+T) was detected through sequencing of amplified DNA. The commonβ-thalassemia mutations at codon 39 (C→T) and at IVS-I-110 (G→A) were also most prevalent among the Tunisian patients, while the milder T→C mutation at IVS-I-6 was not found. All mutations cause a Bd`-thalassemia or a severe B+-thalassemia [T→A at -30; IVS-I-5 (G→A); IVS-I-110 (G→A)] which explains the need for regular blood transfusions in the thalassemia major and S-β-thalassemia patients. Nearly all sickle cell anemia patients carried theβsmutation on a chromosome with haplotype 19 (or Benin) and all had severe anemia with sickling complications. Identification of theβShaplotype was through dot-blot analysis with oligonucleotide probes that detect mutations in theGγandAγpromoter sequences, specific for this haplotype.