The gas-phase structures of five five-carbon monosaccharides (D-ribose, D-lyxose, 2-deoxy-D-ribose, D-xylose, and D-arabinose) were studied via ion-molecule reactions with dimethoxyphosphenium ion and 1,3-dioxolane-2-phosphenium ion in a Fourier transform ion cyclotron resonance mass spectrometer. These reagent ions have been earlier demonstrated to be sensitive to the three-dimensional structures of diastereomeric vicinal diols. They were found to display unique reactivity toward each monosaccharide. The results indicate that the gaseous monosaccharides are cyclic molecules. On the basis of a comparison of the reactions of monosaccharides introduced into the gas phase via two different methods, laser-induced acoustic desorption (LIAD) and thermal desorption, the monosaccharides are concluded to maintain their crystalline structure, a pyranose form, throughout the evaporation procedure. For all the monosaccharides in this study except for D-lyxose, the lowest-energy structure found computationally using density functional theory (B3LYP/6-311++G(d,p)) is a pyranose form that lies at least 1.7 kcal/mol lower in energy than the corresponding lowest-energy furanose form. For D-lyxose, however, a furanose form was calculated to be lower in energy than the pyranose form albeit only by 0.1 kcal/mol. These computational results suggest that a pyranose form indeed is likely to be the dominant form of the monosaccharides in the gas phase. Several possible factors controlling the relative stability of each monosaccharide isomer in the gas phase were examined computationally. The order of importance of these factors in determining the relative stabilities was found to be as follows; intramolecular hydrogen bonding interactions much greater than anomeric > steric (axial/equatorial) factors much greater than Delta2 effect.