Red cell life span within the fetal circulation has not been reported, alth
ough erythrocyte life span has been studied in the adult and newborn. The p
resent study quantified red cell life span in 12 chronically catheterized f
etal sheep at 97-136 days gestation (term = 150 days) with the use of autol
ogous red cells labeled with [C-14] cyanate. Cyanate forms a permanent cova
lent bond with hemoglobin and acts as a permanent red cell label. In the fe
tuses, blood C-14 activity decreased in a curvilinear fashion with time and
reached 50% of the initial activity at 16.4 +/- 1.6 (SE) days. In contrast
, C-14 activity of autologous red cells in two adult ewes decreased linearl
y with time as expected, reached 50% of the initial C-14 activity in 59 day
s, and yielded life spans of 117 and 121 days. Computer modeling and parame
ter optimization taking into account growth and skewed life span distributi
on were used to analyze the C-14 disappearance curve in each fetus. The mea
n life span of all red cells in the fetal circulation was 63.6 +/- 5.8 days
. Mean red cell life span increased linearly from 35 to 107 days as fetal a
ge increased from 97 to 136 days (r = 0.83, P < 0.001). Life span of cells
produced at the time of labeling was significantly greater than the mean li
fe span. Fetal growth rate estimated from parameter optimization was 3.28 /- 0.72%/day; this compared well with the rate of 3.40 +/- 0.14%/day calcul
ated from fetal weights at autopsy. Mean corpuscular volume decreased as a
function of gestational age, but the decrease was small compared with the l
arge increase in red cell life span. We conclude the following: 1) red cell
life span in the fetal circulation is short compared with the adult; 2) re
d cells in younger fetuses have shorter life spans than in near-term fetuse
s; 3) the curvilinear disappearance of labeled red cells in the fetus appea
rs to be due primarily to an expanding blood volume with fetal growth; and
4) red blood cell life span in a growing organism will be significantly und
erestimated unless the expansion of blood volume with growth is taken into
account.