These studies are designed to evaluate the clinical benefits achieved by iron chelation in patients with chronic iron overload. Desferoxamine is administered by subcutaneous infusion and iron removal is determined by measurement of the serum ferritin and periodic non-invasive measurement of liver-iron concentration. Clinical status is evaluated by standard parameters including non-invasive testing of cardiac and endocrine function as indicated by the patient's age and risk category. The study is designed to document the natural history of severe beta thalassemia, treated effectively with regular transfusions and chelation therapy tailored to the patient's clinical status. During the past year we have completed a detailed analysis of our experience with this regimen over the past twelve years. Fifty-nine patients were studied. Liver iron concentration as determined at the end of the study was directly related to the amount of transfusion given and inversely related to the amount of Desferal used during the interval between measurements. The patients were divided into two groups of equal size and clinical characteristics, based on compliance with the chelation regimen. Among patients with a significant iron burden at the time of initiation of chelation, nine of sixteen who were poorly chelated died during the study. There were no deaths among the well-chelated patients. There was also a much higher incidence of impaired glucose tolerance and diabetes mellitus among the poorly chelated patients (60 percent versus 9 percent). These data unequivocally establish the long-term benefits of regular chelation therapy in thalassemic patients requiring blood transfusions. Reversal of cardiac disease has been documented in a total of five patients now on intensive chelation therapy.