We have identified two alpha-globin gene variations in an Arabian male with severe hemolytic disease through sequencing of amplified DNA of his alpha 2- and alpha 1-globin genes. One of the abnormalities involves a CAC (ACC or CCA) deletion between codons 36 and 41 of the alpha 1-globin gene. This leads to the synthesis of an abnormal alpha chain with one instead of two threonine residues at positions 38-39 and to the formation of the unstable Hb Taybe. The second variation is a mutation located in the poly A site of the alpha 2-globin gene (AATAAA-->AATAAG) which is common among Arabian people. Family studies have shown that the two variations are located on opposite chromosomes. The hemolytic disease in this man, resembling Hb H disease, is likely the result of a severe downregulation of both alpha-globin genes on the chromosome with the alpha 2 poly A mutation, and the instability of the alpha-Taybe chain being the product of an alpha 1-globin gene; this leaves only one alpha 2-globin gene normally active.