The most frequent molecular lesions causing alpha-thalassemia are deletions of one or more alpha-globin genes. Detection of these deletions generally requires genomic Southern analysis, which is cumbersome and time consuming. We have designed new sets of primers for PCR identification of the common Mediterranean alpha-globin gene rearrangements, including the -alpha3.7 deletion and the alphaalphaalpha(anti3.7) triplication, the -alpha4.2 deletion, and the --Med allele. We have established reaction conditions that provide easily interpretable, unambiguous diagnoses. Some of the PCR reactions are multiplex, simultaneously identifying several genotypes, thus reducing the time and cost of screening and prenatal testing. The use of these methods should facilitate carrier screening and identification of couples at risk for alpha-thalassemia.