The mechanism and energetics of H-unit (proton, hydrogen, hydride) release from the N-H site of imidazole (IM) is explored on the basis of B3LYP/6-311++G** calculations. Of the three H-unit release modes of IM, H-atom release is strongly favored in the gas phase. Protonation of the bare N-site, positive charge injection over the whole IM ring, and water coupled to the N-H site can each significantly decrease the proton dissociation energy but separately do not change the relative release priority of the proton and H-atom. Their cooperative effect not only significantly decreases the proton dissociation energy but also makes proton release more favorable than H-atom release. A point charge of variable-magnitude placed at the bare N-site leads to a crossover between proton and H-atom dissociation to favor proton release around 1.8 charge units. When a hydrogen-bonded water is added to the N-H site, the crossover that favors proton release falls to a much smaller value (similar to0.4 charge units). Thus, proton release, which is dominant in many normal biological processes, may result from a combination of positive charge or positively-charged particle catalysis at the bare N-site and a basic species assisting at the N-H site.