The chemical characteristics of the polar parts of phospholipids as the main components of biological membranes were investigated by using infrared (IR) spectroscopy and theoretical calculations with water as a probe molecule. The logical key molecule used in this study is methylphosphocholine (MePC) as it is not only a representative model for a polar lipid headgroup but itself has biological significance. Isolated MePC forms a compact (folded) structure which is essentially stabilized by two intramolecular C-H center dot center dot center dot O type hydrogen bonds. At lower hydration, considerable wavenumber shifts were revealed by IR spectroscopy: the frequencies of the (O-P-O)(-) stretches were strongly redshifted, whereas methyl and methylene C-H and O-P-O stretches shifted surprisingly to blue. The origin of both red- and blueshifts was rationalized, on the basis of molecular-dynamics and quantum-chemistry calculations. In more detail, the hydration-induced blueshifts of C-H stretches could be shown to arise from several origins: disruption of the intramolecular C-H center dot center dot center dot O hydrogen bonds, formation of intermolecular C-H center dot center dot center dot O-water H-bonds. The stepwise disruption of the intramolecular hydrogen bonds appeared to be the main feature that causes partial unfolding of the compact structure. However, the transition from a folded to extended MePC structure was completed only at high hydration. One might hypothesize that the mechanism of hydration-driven conformational changes as described here for MePC could be transferred to other zwitterions with relevant internal C-H center dot center dot center dot O hydrogen bonds.