The chemical reactivity of benzene cations in medium-sized (n ∼ 25) (H2O)n water clusters has been investigated. After formation in a supersonic jet, the neutral Bz-(H2O)n species are ionized by resonance-enhanced two-photon ionization. The existence of magic numbers in the mass spectra of these cluster ions has been revealed by reflectron time-of-flight mass spectrometry. These magic numbers are assigned to size-dependent evaporation processes following the ionization. The similarities observed for the present magic numbers compared to those of protonated water clusters allow us to assign them to the formation of a protonated water cluster without ejection of the benzenoid product from the cluster ion. With this diagnosis, we present evidence for the existence of a size-dependent chemical reactivity of benzene cations: a reaction is observed in the medium size range (n ∼ 20−30), whereas small clusters are known not to react. This result is compared to the chemical reactivity of toluene+ in water cluster...