We have developed a rapid approach to detect the two most common alpha-thalassemia-2 (alpha-thal-2) determinants by the polymerase chain reaction (PCR) technique, which takes a few hours to complete. Specific oligonucleotides selectively amplify appropriate segments of the chromosome with the deletion and the normal chromosome under identical experimental conditions, and the products are identified by electrophoresis on 1.5% agarose. Characterization of the two most prevalent types of the -alpha 3.7 determinant [-alpha 3.7(I) and -alpha 3.7(II)] can be made by Apa I digestion of the PCR product. Two types of alpha-thal-2 determinants, -alpha 3.7 and -alpha 4.2, were tested in numerous samples from various parts of the world. This approach is believed to provide a cost-effective way to screen large numbers of blood samples in a relatively short time and can be used to identify alpha-thal-2 heterozygotes and homozygotes and compound heterozygotes (-alpha 3.7/-alpha 4.2) in populations where such alpha-gene defects are shown to exist at high frequencies.