Glutathione peroxidase (GSHPx) activity was found to be greatly elevated in members of a family with alpha-thalassemia. Eleven other families with proven alpha-thalassemia were investigated, and all but one subject with hemoglobin 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.