Red oak borer, Enaphalodes rufulus (Haldeman), a native wood-boring insect, has been indicted as a major contributor to widespread oak mortality in the Ozark National Forest of north-central Arkansas. Little has been published on deciduous tree defenses against wood-boring insects. The objectives of this research were to quantify callous formation in three classes of differentially infested northern red oaks, Quercus rubra L., and investigate constituitive and induced tree defenses between trees in the three red oak borer infestation classes and between three oak species. Total phenolics and protein-binding capacity of winter and summer (control, mechanically wounded and infested) phloem tissues were quantified. High phase liquid chromatography profiles of non-hydrolyzed and hydrolyzed phloem tissues revealed different compounds between tree species and indicate possible differences in amounts of some compounds between infestation classes. We also identified compounds that may be responsible for differential rates of defense-induced borer mortality using mass spectrometry. This research forms the foundation for future research into tree/boring-insect interactions and may provide insight into causes for red oak borer population change.