An epidemiological molecular study was carried out to evaluate the spectrum and allelic frequency of alpha-thalassemia (alpha-thal) defects in Algeria. A series of 153 randomly selected blood donors was screened for 10 alpha-thal alleles described in the Mediterranean area. In addition, six unrelated cases with hematological and biochemical data suggestive of Hb H disease were investigated. Our data revealed an allele frequency of 4.6%. The presence of alpha(0)-thal determinants (-alpha(20.5) and --MED I) was observed both in Hb H patients and in the randomly collected samples. Overall, the -alpha(3.7) deletion was the most prevalent allele (2.9%), followed by the alpha(Nco I)alpha (HBA2:c.1A>G) allele (0.6%) and by the alpha(Hph I)alpha (HBA2:c.95 + 2_95 + 6delTGAGG), -alpha(20.5), --(MED I) alleles (0.3% each). The -alpha(4.2) deletion was observed in only one Hb H patient. These results outline the heterogeneity of the alpha-thal alleles in Algeria which reflects the anthropological history of the country. Because of their frequency, alpha-thal alleles are probably frequent modulators of prevalent beta-globin gene-related hemoglobinopathies in Algeria.