Globin chain synthesis has been studied in 17 patients with thalassemia intermedia, and their relatives, also investigated by routine hematologic and hemoglobinic tests. The mean a/non a ratio was always around 2.20-2.30. In patients with severe thalassemia major, used as a control, the mean a/non a ratio was significantly higher, that is 3.11-3.07. Therefore, the hypothesis that the cause of the lesser severity of the thalassemia intermedia is a lesser imbalance of globin chain synthesis, is suggested. One or both the parents of patients with thalassemia intermedia have mild beta-thalassemia and normal alpha/beta ratio, whereas the parents of patients with severe thalassemia major show a marked beta-thalassemia and a mean alpha/beta ration of 1.76. These data suggest that genes for beta +-thalassemia are responsible for thalassemia intermedia, and genes for beta o-thalassemia are responsible for thalassemia major. In two patients with thalassemia intermedia, the association of an alpha-thalassemia gene with homozygous beta-thalassemia that it is well known to reduce the globin chain imbalance typical of the beta-thalassemia, has also been observed.