The major complication of chronic red cell transfusion is hemosiderosis. One approach to limiting iron infusion is to lengthen the interval between transfusions. Although normal red cell survival is about 110 days, the average unit of blood contains cells of all ages, some of which survive only a few days post-transfusion. If one could prepare a unit containing only young red cells (neocytes), transfusion requirements might be halved. We have used an IBM 2997 cell separator to harvest a cohort of young cells of an average 15-30 days by pyruvate kinase analysis. These cells are frozen and deglycerolized for transfusion into chronically transfused thalassemic patients. To date 51Cr survival data suggest that neocytes circulate up to twice as long as baseline frozen red cells. Clinical status of seven thalassemic patients, supported on neocytes for two years, will be monitored. Part II of this protocol involves removal of senescent red cells (gerocytes) by a similar cell separation technique.