We observed a temporary rise in the percentage of fetal hemoglobin (HbF%) in small preterm infants after cessation of frequent replacement transfusions. We prospectively studied 10 very low birth weight infants, who received frequent transfusions in the first several weeks of life, to determine the influence on oxygen affinity (P₅₀). After cessation of frequent transfusions, those 5 infants whose HbF% increased to the highest values (mean 58%) had a lower oxygen affinity (P₅₀ = 23.3 Torr, p < 0.05) than the remaining 5 infants whose increase in HbF% was less marked, to an average of only 29% (P₅₀ = 24.5 Torr). However, in light of the small difference in P₅₀, we feel that a rise in HbF% by itself after a period of frequent transfusions is unlikely to restrict oxygen delivery except under stressful conditions.