A scanning strategy for the detection of delta-globin gene mutations and polymorphisms is presented. This procedure is based on the denaturing gradient gel electrophoresis (DGGE) of four different artificially amplified DNA fragments which cover the promoter, the exons, as well as IVS I of the reported gene. To estimate the efficiency and sensitivity of the proposed procedure, we analysed the appropriate controls of delta-thalassemic carriers, uncharacterised delta-thalassemias and cases with normal hematological phenotype, but slightly increased (up to 3.5%) HbA2. DGGE results permitted the identification of delta-globin gene mutations and the polymorphism -199 (T-->C). Three novel base substitutions inside the promoter region of the gene [-65 (A-->G), -55 (T-->C), -36 (C-->A)], were also revealed. These changes are either linked in cis with other mutations or are responsible for thalassemias or for positive regulatory effect in delta-globin gene expression. The proposed experimental strategy consists of an accurate, rapid, safe and inexpensive screening procedure for establishing the molecular basis of delta-globin gene defects, suitable for the application for both research and diagnostics.