Multi-photon ionisation (MPI) and electron impact ionisation (EII) mass spectrometry experiments have been carried out to probe unimolecular and intermolecular reactivities in hydrated adenine clusters. The effects of clustering with water on fragment ion production from adenine have been studied for the first time. While the observation of NH4+ fragments indicated the dissociation of protonated adenine, the dominant hydration effects were enhanced C4H4N4+ production and the suppression of dissociative ionisation pathways with high activation energies. These observations can be attributed to energy removal from the excited adenine radical cation via cluster dissociation. Comparisons of MPI and EII measurements provided the first experimental evidence supporting hypoxanthine formation in adenine–water clusters via theoretically predicted barrierless deamination reactions in closed shell complexes.