479 families, each with a proband affected by homozygous beta-thalassemia, were typed for HLA. 224 families with a total of 1020 members were typed for the HLA-A, B, C, DR and DQ loci and 255 families with 1046 family members, were typed for the HLA-A, B, and C loci. Altogether, 896 A, B, C, DR and DQ haplotypes and 1020 A, B and C haplotypes were defined. At the same time, 120 healthy unrelated individuals from the same population were typed and used as controls. The analysis of the results was carried out at antigen, allele, haplotype, genotype and sex ratio level with the aim of looking on the one hand, for the existence of heterogeneity between the probands, the unrelated individuals and the healthy siblings and, on the other, for the existence of any distortion whatsoever of the HLA segregation in either the probands or in the healthy siblings in respect of the expected values according to the Mendelian equilibrium. No significant differences were evident between the probands and the controls by the tests carried out at different levels of the HLA system. This leads us to exclude the existence of an association between beta-thalassemia and HLA in the population studied. Moreover, the analysis of the transmission of the alleles, the haplotypes, the genotypes and the sex-ratio by parents to both affected and to healthy children did not show any clear evidence of segregation distortion in respect of the theoretical values.