The first and second ionization energies of trimethyl substituted analogs of benzene and pyridine are determined by means of mass spectrometry in conjunction with synchrotron radiation. The first ionization energy of 1,3,5-trimethylbenzene amounts to (8.38 ± 0.05) eV and the second ionization energy to (22.8 ± 0.1) eV. The first ionization energy of 2,4,6-trimethylpyridine is determined as (8.65 ± 0.05) eV and the second ionization energy as (23.0 ± 0.1) eV. The ionization energies are compared with those of unsubstituted benzene and pyridine and the effects of the methyl groups are evaluated by means of isodesmic reactions. As expected, it is found that the electron-donating effect of the methyl groups stabilizes neutral pyridine and doubly charged pyridine more than neutral benzene and doubly charged benzene, respectively. Surprisingly, the opposite effect is found for the radical cations, which is ascribed to the unfavorable degenerate electronic structure of benzene radical-cation, which disappears upon the methyl substitution.