The solvent dependences of the populations of the hydroxymethyl rotamers of methyl 2,3,4,6-tetra-O-[2H3]-α-d-glucopyranoside (2a) and methyl 2,3,4-tri-O-[2H3]-α-d-glucopyranoside (6) in 10 and 8 solvents, respectively, have been determined by analysis of 3 J H5,H6R and 3 J H5,H6S values and by consideration of evidence for hydrogen bonding through infrared spectroscopy and 3 J H,OH values. The methods used to determine coupling constants in individual hydroxymethyl rotamers were reexamined, and an improved protocol was developed. When O-6 is methylated (2a), the populations of the hydroxymethyl rotamers are largely independent of solvent polarity at ratios of about 61:38:0 gg:gt:tg, except that a small population (<4%) of the tg rotamer appears in the most polar solvents at the expense of the gg rotamer. When O-6 is unsubstituted (6), there are substantial changes in rotamer population as solvent polarity increases due to loss of intramolecular hydrogen bonding and stabilization of the more polar rotamers. The rotamer populations for 6 return to those adopted by the permethylated derivative (2a) in the most polar solvents. It was concluded that hydrogen bond donation from OH-6 to water is not important in determining hydroxymethyl rotational preferences. The well-known “reversed” chemical shift order of the two C6 protons of peracetylated glucopyranose derivatives was shown to also occur for permethylated derivatives and is ascribed to solvent effects in addition to anisotropy. The solvent effect on the chemical shift difference is attributed to the fact that one of the two protons stays on the same side of the pyranose ring in the two more populated rotamers while the other proton exchanges environments.