The proximal heme axial ligand plays an important role in tuning the reactivity of oxoiron(IV) porphyrin pi-cation radical species (compound I) in enzymatic and catalytic oxygenation reactions. To reveal the essence of the axial ligand effect on the-reactivity, we investigated it from a thermodynamic viewpoint. Compound I model complexes, (TMP+center dot)(FeO)-O-IV(L) (where TMP is 5,10,15,20-tetrarnesitylporphyrin and TMP+center dot is its pi-cation radical), can be provided with altered reactivity by changing the identity of the axial ligand, but the reactivity is not correlated with spectroscopic data (nu(Fe=O), redox potential, and so on) of (TMP+center dot)(FeO)-O-IV(L). Surprisingly, a clear correlation was found between the reactivity of (TMP+center dot)(FeO)-O-IV(L) and the Fe-II/Fe-III redox potential of (TMP)(FeL)-L-III, the final reaction product. This suggests that the thermodynamic stability of (TMP)(FeL)-L-III is involved in the mechanism of the axial ligand effect. Axial ligand-exchange experiments and theoretical calculations demonstrate a linear free-energy relationship, in which the axial ligand modulates the reaction free energy by changing the thermodynamic stability of (TMP)Fe-III(L) to a greater extent than (TMP+center dot)(FeO)-O-IV(L). The linear free energy relationship could be found for a wide range of anionic axial ligands and for various types of reactions, such as epoxidation, demethylation, and hydrogen abstraction reactions. The essence of the axial ligand effect is neither the electron donor ability of the axial ligand nor the electron affinity of compound I, but the binding ability of the axial ligand (the stabilization by the axial ligand). An axial ligand that binds more strongly makes (TMP)Fe-III(L) more stable and (TMP+center dot)(FeO)-O-IV(L) more reactive. All results indicate that the axial ligand controls the reactivity of compound I (the stability of the transition state) by the stability of the ground state of the final reaction product and not by compound I itself.