The reversible and stable binding of molecular oxygen to the heme iron(II) is the basis of hemoglobin function. However, the oxygenated form of hemoglobin, as well as of myoglobin, is known to be oxidized easily to the ferric(III) met-form, which cannot bind dioxygen and is therefore physiologically inactive, with generation of the superoxide anion. In this autoxidation reaction, human oxyhemoglobin (HbO₂) shows a biphasic curve containing the two rate constants, a fast one due to the α chains and a slow one for the β chains, respectively. Such a chain heterogeneity could be maintained even in the low concentrations of hemoglobin corresponding to appreciable dissociation into αlβl and α2β2 dimers. When the α and β chains are separated from the HbO₂, both chains were oxidized much more rapidly than in the tetrameric parent, and become freed from their rate differences over the wide range of pH 5-11. These recent new findings have led us to conclude that the formation of the αlβl or α2β2 contact suppresses remarkably the autoxidation rate of the β chain and thus plays a key role in stabilizing the HbO₂ tetramer. On the basis of the two different types of the αβ contacts defined in the molecule, we will finally form a unified picture of hemoglobin function by a new paradigm for reconciling the cooperative oxygen binding with the stabilization of the bound dioxygen.