Iron(II/III)porphyrin/cyclodextrin inclusion complexes serve as hemoprotein models in vivo. Here we showed the iron(III)porphyrin complex to be spontaneously reduced to its iron(II) state in mouse circulation. The reduced complex bound endogenous CO from carboxyhemoglobin, which was followed by urinary excretion. The natural reduction system was found to be effective for synthetic heme-model compounds.