Host-guest binding sometimes triggers the subsequent chemical reactions of the host framework as well as changes in the physical properties. Since the host-guest binding generally occurs very quickly, it is sometimes difficult to differentiate the mechanism from the alternative one in which the guest binding occurs after the reaction. However, it is important to differentiate the two mechanisms when we Reaction site develop new molecules based on time-dependent functions. PiP Thus, we propose two distinct mechanisms, recognition first and reaction first, in a slowly reacting host system. We designed and synthesized a new cobalt(III) metallohost, [LCo2(pip)(4)](OTf)(2) (pip = piperidine), which can take up a guest cation into its 18-crown-6-like cavity causing concomitant exchange of the axial piperidine ligands under solvolytic conditions. We investigated the mechanism to elucidate whether the guest recognition or ligand exchange occurs first. When Na+ (5-10 equiv) was present, the guest recognition occurred by the recognition first mechanism; i.e., Na+ was initially taken up into the cavity, then the axial piperidine ligands were replaced with methoxo ligands. On the other hand, when 1 equiv of M+ (= K+, Rb+) was present, the guest recognition occurred by the reaction first mechanism; i.e., M+ was taken up after one of the piperidine ligands was replaced with a methoxo ligand. Therefore, the recognition pathway can be switched by changing the guest cations.