Glutathione peroxidase (GSHPx) activity was greatly elevated in members of a family with .alpha.-thalassemia. Eleven other families with proven .alpha.-thalassemia were investigated, and all but 1 subject with Hb H disease had increased red cell GSHPx. Most persons with .alpha.-thalassemia trait also had increased activity of red cell GSHPx. In contrast, only very modest increases in glutathione peroxidase activity were observed in subjects with various forms of .beta.-thalassemia.