Summary We describe a simple approach for molecular characterization and locus assignment of structural mutants by direct sequencing of enzymatically amplified DNA selective to α1 and α2 globin gene regions. Nucleotide substitution of two structural variants (Stanleyville II α278Lys and J Mexico α254Glu) 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 α globin structural variants and most of the nondeletion α thalassaemic mutants should be characterizable by this approach.