A sequential model for the basis of co-operativity in multimeric binding proteins, originally presented as a description of oxygen binding to each of the haem groups of the haemoglobin tetramer. Unlike in the earlier Monod-Wyman-Changeux concerted model, each monomer may assume a low-affinity or a high-affinity conformation. A high-affinity ligand-bound monomer favours the high-affinity conformation of adjacent unbound monomers. In the absence of a ligand (oxygen in the case of haemoglobin) the subunits exist in a low-affinity 'taut' conformation. The ligand may bind to as many as two monomers in this conformation, at which point all four monomers convert from the low-affinity form to the high-affinity 'relaxed' conformation.