A family has been observed in which aβthalassemia determinant is inherited over three generations together with high Hb F level (8–12 %) and increased number of fetal-hemoglobin-containing-cells (F-cells). The values of red cell indices and globin chain synthesis ratios, yet typical ofβthalassemia, were significantly shifted to the normal values when compared with those of typicalβthalassemia heterozygotes belonging to the same family group. The occurrence in these individuals of a heterocellular hereditary persistence of fetal hemoglobin (HPFH) determinant and its linkage relationship with theβthalassemia is discussed. In the third generation two adult individuals wereβthalassemia homozygotes having inherited aβthalassemia determinant from one parent and aβthalassemia together with the HPFH determinant from the other. They showed an extremely mild clinical condition, and 11–12 g/dl of mainly Hb F without having ever required blood transfusions. Virtually all the red cells were F-cells in both subjects. The importance of the coexistence of HPFH determinants capable of increasing the size of the F-cell population in patients affected by homozygous thalassemia is discussed, considering the sensible benefit which derives from enhanced Hb F production in this syndrome.