Ab initio molecular orbital calculations have been used to study the effect of ring distortion on the outcome of protonation of 2-methoxyoxane and 2-methylsulfanyloxane in the gas phase. Protonation of the skew conformations of equatorial 2-methoxyoxane results in spontaneous collapse to the oxocarbenium ion, whereas the skew conformations of equatorial methyl(2-oxanyl)sulfonium exist as stable species. The chair conformation of the axial anomer of methyl(2-oxanyl)sulfonium is also found to exist as a stable species, unlike the axial anomer of methyl(2-oxanyl)oxonium, which collapses spontaneously to the oxocarbenium ion. These results are discussed in relation to the stability of thioglycosides toward cleavage by glycosyl hydrolases.