SummaryOne to 4 days before birth of their litters, pregnant buffalo rats were injected intravenously with 200 μCi of [2-14C]glycine in order to label a cohort of fetally produced red blood cells (RBC). Shortly after birth, the newborn rats were transferred to noninjected foster mothers, and RBC survival was determined by the rate of production of14CO in the expired air of the newborn animals. In separate experiments, pregnant rats were injected 1–2 days before birth of their litters; blood was collected from the newborn at 5 days of age, washed, transfused into normal adult hosts, and RBC survival determined from the resultant14CO production. When compared with adult RBC,in situsurvival of fetally produced RBC was 22% of normal (mean life span of 12.1 days in the fetus, and 54.5 ± 1.5 (SE) days in the adult). This shortening of survival resulted from an acceleration of RBC senescence (15.7 days for fetal RBC and 66.2 ± 0.7 days for adult RBC) and an increased rate of random hemolysis (3.70%/day in the fetal RBC and 0.67 ± 0.07%/day in adult RBC). Although cross-transfusion of adult RBC into compatible adult rat hosts resulted in only a modest shortening of RBC lifespan (mean RBC survival reduced from 54.5 ± 1.5 days to 52.8 ± 0.8 days), similar treatment of fetally produced RBC resulted in a marked acceleration of senescence from 15.7 days to 5.8 days. Examination of the RBC survival curves for those litters injected less than 72 hr before birth indicated the presence of an additional population of cells with survival in the range of 25–40 days. The proportion of cells surviving longer than the major cohort (but shorter than times characteristic of adult RBC) increased as the time interval between isotope injection and birth decreased.SpeculationThe magnitude of the shortening in survival noted for fetal RBC suggests the presence of structural and/or metabolic alterations peculiar to these cells, rather than alterations secondary to increased erythropoietic rate alone.