The strategy for early prenatal diagnosis of beta-thalassemia in Singapore by direct detection of the mutant beta-globin gene requires the spectrum of mutations producing the disorder in this population to be characterized. We analyzed 134 beta-thalassemia alleles from Singapore by specific oligonucleotide hybridization after DNA amplification, using a nonradioactive enhanced chemiluminescence detection system. The mutations were identified in 90% of the alleles using five oligonucleotide probes for the following mutations: codons 41/42 (deletion-TCTT), IVS II nt 654 (C-->T), codon 17 (A-->T), IVS I nt 5 (G-->C), and -28 TATA box (A-->G). Together with the strategy of direct sequencing, a total of 97% of the mutations were identified. In the Chinese subpopulation, 97% of the mutations were detected by the oligonucleotide probes. Using just four oligonucleotide probes would identify 96% of the mutations, and 76% of the mutations were accounted for by codon 41/42 (-TCTT) and IVS II nt 654 (C-->T) mutations. Thus in this subpopulation early prenatal diagnosis would be possible in virtually all the affected families.