The numerous investigations that have focused on the iron binding site to explain the different affinity of hemoglobin for CO and O-2 are still without success. Thus, this work addresses the problem of nonlocal effects, which have been disregarded so far. We have investigated the protein behavior in relation to the iron-ligand nature. The present data Show that different parts of the protein, which are not in close contact with the heme pocket, are effectively influenced by the nature of the iron-ligand bond. Whereas oxyhemoglobin and carbonmonoxide hemoglobin in solution exhibit the same molecular shapes and helical contents, different electrostatic interactions in association with a redistribution of the strains occur in the protein matrix. Due to electric couplings of the heme to the protein, the whole molecule is sensitive to the chemical nature of the iron-ligand bond. This suggests that long distance electrostatic interactions promote the energy transduction through the protein molecule.