Restriction enzyme analysis of the a and { globin genes was carried out in four cases of Hb Bart's hydrops fetalis, in three patients with Hb H disease without Hb CoSp, in three patients with Hb H disease with Hb CoSp, in 47 individuals with a thalassemia trait, and in 47 normal individuals. All four cases of Hb Bart's hydrops fetalis resulted from deletions of a1 and a2 globin genes which did not extend to the ${1 and fl globin genes. The same type of deletion was observed in a thal, carriers, but two newborns (one Malay and one of Chinese extraction) had a nondeletion type of a thal, which was confirmed by quantitative aglobin gene analysis. In addition, two other newborns diagnosed as a thal, trait carriers (one Malay, one Chinese) were shown to have a deletion of both a globin genes by quantitative a globin gene analysis, but further testing with { globin gene probe failed to reveal an abnormal fragment length characteristic of an a globin gene deletion. We believe that this last condition is due to a large deletion which includes all a globin genes and all { globin genes on the same chromosome. On another front, Bgl I1 restriction analysis of all four Hb Bart's hydrops fetalis cases and the a thal, trait carriers showed a 10.5-kb Bgl I1 restriction fragment, in the hydrops fetalis as a single band, while in the carriers this 10.5-kb fragment was accompanied by the usual normal 12.5-kb and 11.3-kb fragments. We report that this 10.5-kb fragment, previously thought to be specific for the Southeast Asian a thal, gene deletion, is also common in normal individuals. Nevertheless, digestion with other enzymes can clearly differentiate the a thal, and normal genotypes. We distinguish the findings in the a thalassemias from the extensive DNA polymorphism in the region of the a and { globin genes.