We studied the three-way interaction of elevated CO2, nitrogen (N), and temperature (T), and the two-way interaction of elevated CO2 and early-season defoliation on the secondary chemistry and resistance of Eurasian silver birch (Betula pendula) and North American paper birch (B. papyrifera) against the Eurasian hare (Lepus timidus) and the North American eastern cottontail rabbit (Sylvilagus floridanus), respectively. Elevated CO2 decreased the palatability of winter-dormant silver and paper birch stems to both hares and rabbits, respectively. But the effect on hares was only apparent at intermediate levels of N fertilization. Elevated T had no effect on palatability. The effects of elevated CO2, N, and T on levels of silver birch bark phenolics and terpenoids were dominated by two-way interactions between N and CO2, and N and T. Generally, however, N amendments elicited a parabolic response in carbon partitioning to most biosynthetic classes of silver birch phenolics (i.e. highest concentrations occurring at intermediate N). CO2 elevation was most enhancing at highest levels of N. On the other hand, T increases, more often than not, elicited reductions in phenolics, but especially so at the highest N level. In the case of B. papyrifera, elevated CO2 increased carbon partitioning to Folin-Denis stem and branch phenolics and condensed tannins. Early-season defoliation, on the other hand, had no effect on phenolics and tannins but lowered both N and energy levels of branches. Elevated CO2 substantially ameliorated the negative effects of severe defoliation on tree growth. These results support the hypothesis that continuing anthropogenic alterations of the atmosphere may trigger significant changes in plant phenotypic resistance to mammalian herbivores owing to an increasing net carbon balance between the highly vagile supply and demand capacities of plant carbon sources and sinks.