Effects of permethylation on disaccharide conformation were studied with relaxed-residue phi,psi maps for eight disaccharides of glucose and their permethylated derivatives. Many orientations of the methyl groups were generated with the conformation generator in the Chem-X software program and filtered with a rules-based method. For native molecules, clockwise and counterclockwise rings of hydrogen bonds were also used. MM3(96) energies were calculated with a dielectric constant (epsilon) of 1.5. The native disaccharide maps were also calculated at epsilon = 3.5 and 7.5 to reduce hydrogen-bonding strength. Maps for native and permethylated structures were generally similar. The permethylated structures, which do not make hydrogen bonds, gave maps that were most similar to the native maps that had reduced hydrogen-bonding strength. All phi,psi values for the global minima of the permethylated models fell within the 1-kcal/mol contours on the epsilon = 7.5 maps. Flexibility values based on a partition function were substantially less for permethylated alpha,alpha-trehalose and laminarabiose, compared to their native counterparts at any epsilon. On the other hand, strong interresidue hydrogen bonding at epsilon = 1.5 for the global minimum structures of cellobiose and maltose caused those models to be more rigid than their permethylated counterparts. All permethylated models were less flexible than their native counterparts at epsilon = 7.5 and their backbone analogues based on tetrahydropyran calculated at epsilon = 1.5.