In order to clarify the reasons for the reduced Hb A2levels in Sardinianδβ-thalassemia, we characterized, both by cloning and sequence analysis and by direct sequencing of amplified DNA, theδ-globin gene from an individual of Sardinian descent who is a compound heterozygote for theββ-thalassemia codon 39 (C→T) nonsense mutation and the Sardinianδβ-thalassemia [codon 39(C→T)/ -196(C→T)Aγ]. The analysis of theδ-globin gene from theδβ-thal-assemia chromosome revealed an entirely normal sequence. The defective function of theδ-globin gene in this determinant is thus likely related to a suppressive effect of the in cis nondele-tional high persistence of fetal hemoglobin mutation of the Aγgene, probably resulting from an increased capability of the relative promoter to interact with the locus control region.