To determine whether the high oxygen affinity of fetal blood, compared with that of the adult, is advantageous to the fetus during fetal anemia we studied 16 chronically catheterized fetal lambs. Half of the lambs had hemoglobin-oxygen affinity reduced acutely by isovolemic exchange transfusion with fresh adult whole blood; the other half served as controls. In both groups of fetuses, we measured fetal oxygen delivery, oxygen consumption, and acid-base state at normal fetal hematocrit levels and during reductions in the hematocrit level of 30% (moderate anemia) and 60% (severe anemia) produced by isovolemic exchange transfusions with plasma. At normal fetal hematocrit levels, reductions in hemoglobin-oxygen affinity had no effect on fetal oxygen consumption or acid-base state. During moderate anemia, fetal oxygen delivery decreased in both series of fetuses, but oxygen consumption and base excess fell only in those fetuses whose circulations contained adult hemoglobin. During severe anemia, oxygen consumption and base excess decreased in both groups of fetuses, although these changes were more pronounced in fetuses with adult hemoglobin than in those with fetal hemoglobin. Our data indicate that, even though a high hemoglobin-oxygen affinity may not be essential to a healthy fetus, it is critical for normal metabolism in a fetus subjected to a hypoxic stress such as anemia.