Examination of some trends and differences between acetonitrile/water and methanol/water mixtures has been carried out. These systems are of interest for chromatographers since they are common mobile constituents. Some differences in the molecular arrangement of these solvents were observed from NMR and IR results. These observations might be of use in understanding and developing chromatographic separations. IR studies revealed C-H bond compression in methanol compared with acetonitrile which indicates different molecular arrangement in their aqueous mixtures. NMR and IR results show a clear non-linear behaviour in molecular arrangement. This justifies the deviation of methanol and acetonitrile aqueous solution from the norm. However, both solvents showed similar ionization suppression effects on examples of weak acids and bases.