The molecular defect was defined in 38 delta beta-thalassemic chromosomes from 30 unrelated heterozygous and 4 homozygous patients of Greek origin. Restriction fragment beta-gene cluster haplotypes were studies in 23 delta beta-thalassemic chromosomes. The molecular lesion was identical in all studied cases and corresponds to the 'Sicilian' type of delta beta-thalassemia. Restriction haplotypes analysis has shown that, with one exception only, all Greek delta beta-thalassemic chromosomes bear the polymorphic sites which characterize haplotypes I or VII, the former being probable by indirect evidence. The striking similarities of the molecular lesion and the underlying haplotypes are consistent with two theories: (1) The deletion occurred once on a chromosome and spread all over Greece and the Mediterranean area thereafter; (2) the 5' subhaplotype +----favors the deletional event in the delta-beta gene area.