Significance: The conduction of protons through the highly restricted paths of transmembrane proteins is an essential process of living systems and an intriguing problem in modern physical chemistry. The small size of the influenza M2 proton channel makes it an ideal system for the study of proton transport across a membrane. Additionally, the M2 channel has medical relevance as an anti-flu drug target. These high-resolution structures of the channel were obtained by crystallizing the protein in a membrane-like environment and reveal networks of hydrogen-bonded waters that change with temperature and pH. The locations of these waters, in conjunction with molecular dynamics simulations that predict their hydrogen bond orientations, provide insight into the mechanism of proton stabilization and transduction within the channel.