Ground-state tautomerism and excited-state proton transfer of 4,5-dimethyl-2-(2＇-hydroxyphenyl)imidazo (DMHI) was investigated by means of UV-vis absorption spectroscopy, by steady-state and time-resolved fluorescence spectroscopy, and by quantum mechanical calculations. The behavior of DMHI in ethanol and water was studied in neutral, acidic, and basic conditions. Three ground-stale species were detected in neutral solutions of DMHI: the cis-enol form with an intramolecular hydrogen bond, the trans-enol form that is hydrogen bonded to the solvent, and the keto tautomer. The relative proportions of these species depend strongly on the solvent: the keto tautomer was not detected in ethanol, whereas this tautomer is the predominant species in neutral water, where negligible amounts of the cis-enol form, exist. These experimental findings could be reproduced by quantum mechanical calculations up to the B3LYP/6-311+G** level of theory combined with semiempirical calculations of solvation free energies, which allowed the energy diagram in the gas phase and in solution to be known. A combination of the supermolecular approach and the SMx methodology was necessary to account fur the differential solvation of the different isomers in neutral aqueous solution. In the excited slate, the cis-enol form always undergoes the fast excited-state intramolecular proton transfer to yield the keto tautomer. Upon photoexcitation of the trans-enol form and the keto tautomer, no excited-state reaction takes place. In acidic media, the photoexcited cation suffers deprotonation of the hydroxyl group, yielding the excited keto tautomer.