Rearrangement of hydrogen bonds in the protonated methanol-water cluster ion H+(CH3OH)(4)H2O is analyzed. The analysis, based on ab initio calculations performed at the B3LYP/aug-cc-pVTZ//6-31+G* and MP4/ 6-311+G*//B3LYP/6-31+G* levels of computation, provides information about potential minima, transition states, and pathways for the hydrogen bond rearrangement processes. Results of the analysis are compared systematically to the experimental measurements for H+(CH3OH)(4)H2O, where two distinct charge-centered (H3O+ and CH3OH2+) isomers have been identified in a supersonic expansion by fragment-dependent vibrational predissociation spectroscopy (Chaudhuri et al. J. Chem. Phys. 2000, 112, 7279). Revealed by the calculations, the lowest energy pathway for the, transition from an open noncyclic hydronium-centered isomer [H3O+(CH3OH)(4)] to a linear methyloxoium-centered isomer [CH3OH2+(CH3OH)(3)H2O] involves three stable intermediates and four transition states. The transition can go through either all four-membered ring isomers or,a mixture of four-membered and five-membered ring intermediates. The latter is an energetic ally more favorable process because of less strain involved in the five-membered ring formation. A barrier height of < 2.5 kcal/mol (after zero-point energy corrections) is predicted, suggesting that rapid interconversions; among different isomers can occur at room temperature for this particular cluster cation.