Transfusion of donor blood containing predominantly younger red cells with prolonged survival in vivo could significantly reduce the iron overload of patients requiring chronic transfusion. Age-dependent separation of red cells can be obtained by buoyant density centrifugation on isotonic solutions of arabino-galactane. By this technique, rabbit red cells were separated on a single layer of arabino-galactane and the appropriate fraction, after being labeled with (51)Cr, was reinfused into the donor. The survival in vivo was calculated by a mathematical model which corrects for both (51)Cr elution and random loss. There was a significant difference in survival in vivo between the light young red cells and the heavy old red cells. The potential survival in vivo of the 50% lightest red cells was 56 days, compared to 28 days for the heaviest red cells. Arabino-galactane appeared to be devoid of acute toxicity and of strong antigenicity and it did not appear to adhere to the red cell stroma. These data extrapolated to humans indicate that it may be feasible and advantageous to use red cells fractionated by this technique for transfusion. The 50% lightest human red cells can be expected to have a mean survival of 88 days, compared with 60 days for unfractionated blood. Transfusion of young red cells could significantly reduce the iron overload for patients requiring chronic transfusion, by avoiding infusion of the oldest red cells, which contribute equally to iron overload yet offer only transient survival in vivo.