A relation between the heat of formation of molecular ions and cation size is used to study the effects of methyl substitution on a series of species containing oxygen. These include methanol, the hydroxymethyl radical, formaldehyde and related isomers, acetaldehyde and related isomers, ketene, formic acid, and acetic acid. This size-dependent relation is found to be valid in most cases, enabling a choice to be made among conflicting reported ion and neutral heat of formation values, but it holds much less well in methyl-substituted formaldehyde and its carbene isomers. The cations formed in methanol, hydroxymethyl, hydroxycarbene, and formic acid by methyl substitution at carbon sites were found to be more stable than those substituted at oxygen sites. Suggestions are made for investigating or reinvestigating the ionization energies and the heats of formation of several of the molecules studied in cases where multiple choices are available in the literature or where our analysis suggests that more reliable values are needed.