Hemoglobin (Hb), an oxygen-carrying protein, has an ot alpha(2)beta(2) tetrameric structure that dissociates reversibly into two alpha beta dimers (alpha(2)beta(2) reversible arrow 2 alpha beta). We synthesized a cyclic Hb-ring monomer with two beta subunits bound through a 10 kDa polyethylene glycol (PEG) chain. The monomer induced ring-opening polymerization to produce a supramolecular polymer alpha beta intersubunit interaction of afi dimers of an Hb molecule at the PEG terminals. Both the ring-closed monomer and the ring-opened supramolecular polymer were then fixed covalently by intramolecular cross-linking of two beta subunits. Quantification of fixed products at various monomer concentrations revealed the equilibrium constant (K), a ratio of propagation and depropagation rate constants, as 5.68 mM(-1). The average degree of polymerization ((DP) over bar) increased proportionally, concomitantly with the initial monomer concentration. Hb polymer with (DP) over bar = 13.2 (M-n = ca. 1 MDa) was obtained by cross-linking at 2.33 mM. Our novel strategy of ring-opening polymerization of Hb will eventually realize a highly aligned and efficiently polymerized Hb for creating artificial oxygen carriers for a clinical use.