1 Genetic variation in the phytochemical responses of plants to CO2 enrichment is likely to alter trophic dynamics, and to shift intraspecific selection pressures on plant populations. We evaluated the independent and interactive effects of atmospheric CO2 and quaking aspen (Populus tremuloides Michx.) genotype on chemical composition of foliage and performance of the whitemarked tussock moth (Orgyia leucostigma J. E. Sm.). 2 This research was conducted at the Aspen FACE (Free Air CO2 Enrichment) site in northern Wisconsin, U.S.A. Leaf samples were collected periodically from each of three genetically variable aspen genotypes growing under ambient and elevated CO2, and analysed for levels of primary and secondary metabolites. Tussock moth larvae were reared in situ on experimental trees, and development times and pupal masses were recorded. 3 Foliar chemical composition varied among aspen genotypes and in response to CO2 enrichment. However, chemical responses of trees to elevated CO2 were generally consistent across genotypes. 4 Larval development times varied among host genotypes and increased slightly for insects on high-CO2 plants. Enriched CO2 tended to reduce insect pupal masses, particularly for females on one of the three aspen genotypes. 5 CO2 × genotype interactions observed for plant chemistry and insect performance in this study with a small number of genotypes are probably too few, and too weak, to shift selection pressures in aspen populations. These results differ, however, from earlier work in which more substantial CO2 × genotype interactions were observed for plant chemistry.