The physiological significance of the cooperativity of human hemoglobin (Hb) is considered from the viewpoint of the effectiveness of the Bohr shift at the sites of O₂ release and uptake across the placental membrane. The effects of the Bohr shift was examined by changing the O₂ saturation of Hb (S(pO2)) per unit change in P₅₀, -dS(PO2)/dP₅₀, where P₅₀ is partial pressure of O₂ at half saturation. The Bohr shift at the sites of O₂ uptake and release was found to be highly effective in both fetal and maternal bloods at physiological degree of cooperativity (Hill's coefficient, n=2.65). From the results obtained in this paper, it is concluded that the positions of OECs of fetal and maternal Hbs are regulated to receive a maximal benefit from the Bohr shift, and that a relatively low n value of human tetrameric Hb is adequate for the O₂ and CO₂ exchange across the placental membrane.