The high prevalence of beta-thalassemia in Southeast Asia is a major public health problem. Development of genetic counseling and prenatal diagnosis programs is a priority. To provide the groundwork for such programs in South Vietnam, we determined the spectrum of beta-thalassemia mutations in 35 severely affected patients and their relatives. We identified six different beta-thalassemia alleles (five beta(0) and one beta(+) mutations), in addition to the common mutation at codon 26 (GAG --> AAG) responsible for Hb E. These data provide insights into the distribution of beta-thalassemia alleles in the Vietnamese population.