Family studies were performed in 10 patients from seven different families with homozygous beta zero thalassaemia intermedia and in three patients with homozygous beta+ or compound heterozygous beta+ and beta zero thalassaemia intermedia. In nine of the 10 families at least one of the parents was found to have raised Hb A2 and Hb F. In the heterozygotes with increased Hb A2 and Hb F, the means of Hb F and MCV were significantly higher than those observed in regular Hb A2 thalassaemia heterozygotes. However, the severity of imbalance in in vitro haemoglobin synthesis was similar in these two groups. The imbalance in the alpha/non-alpha synthetic ratio was heterogeneous in the patients, being 2.1 and 4.0. Segregation of the raised Hb F from the Hb A2 beta thalassaemia determinant was found to be possible in only one of the 36 heterozygotes. This may exclude the possibility of the presence of an additional determinant responsible for the activation of the gamma chain. The G gamma/A gamma ratio of Hb F was that of the fetal type (G gamma was between 50 and 71% of the total gamma chain). The A gamma T variant of gamma chain was not detected in cis of the beta zero thalassaemia determinant characterised by increased Hb F and Hb A2. A retrospective study of 180 patients with beta thalassaemia and their parents indicated that the combined rise in Hb A2 and Hb F was more common in the heterozygous parents (11 out of 30 parents) of the patients with beta zero thalassaemia than it was in the parents of patients with beta+ thalassaemia (three out of 140 parents). The presence of increased Hb A2 and Hb F in the heterozygote may in some cases determine the relative mildness of the disease.