Because of their high prevalence throughout the world, alpha-thalassemia and hemoglobinopathies often occur in the same individual. Southern blot hybridization analysis of the alpha-globin gene cluster permits the detection of the common deletion alpha-thalassemias and the definition of the phenotypes affiliated with the interactions of alpha-thalassemia and hemoglobinopathies. Important insights into the pathophysiology of Hb SS have been gained, and the nature of the perturbation of heterozygous hemoglobinopathies by alpha-thalassemia has been established.