We describe a simple approach for molecular characterization and locus assignment of structural mutants by direct sequencing of enzymatically amplified DNA selective to alpha 1 and alpha 2 globin gene regions. Nucleotide substitution of two structural variants (Stanleyville II alpha 2(78Lys) and J Mexico alpha 2(54Glu) were determined and their encoding loci were specified. The amplified segment encompasses sequences upstream of the CAAT box to downstream of the Poly(A) addition signal. Hence all of the alpha globin structural variants and most of the nondeletion alpha thalassaemic mutants should be characterizable by this approach.