Anemic, critically ill newborn infants are among the most frequently transfused groups of patients in the US. An estimated 130,000 infants annually receive approximately 1,000,000 RBC transfusions. Unlike adults, important data are lacking regarding the transfusion product for optimal RBC survival in infants. Contributing to this lack are two major recent changes in neonatal blood banking and transfusion practices. These are 1) the use of transfused adult donor blood stored for up to the 42 day FDA limit instead of only using blood stored for less than 7 days as had been done previously; and 2) potential use of the infant's own blood harvested from the placenta to avoid the risks of viral infections and immune transfusion reactions from donor blood. Unfortunately, there are no definitive infant studies that address these changes by directly measuring RBC survival. Such infant studies have been hampered by technical problems. Specifically, RBC survival data must be adjusted for growth, laboratory phlebotomy loss, and intervening additional RBC transfusions but in practice have not. Moreover, safety issues have precluded many infant RBC survival studies (eg, exposure to 51Cr radioactivity and removal of too much blood from today's tiny, premature infants). Indeed, prior to 1970 (the end of using 51Cr as a RBC label in infant RBC survival studies), infants weighing less than 1,500 g at birth did not often survive, and RBC survival data do not exist for today's smallest, most frequently transfused infants whose birth weights are 500-1,000 g.