Conium maculatum, a Eurasian weed naturalized in North America, contains high concentrations of piperidine alkaloids. In the United States, C. maculatum was largely free from herbivory until approximately 30 years ago, when it was re-associated with a monophagous European herbivore, the oecophorid caterpillar Agonopterix alstroemeriana. At present, A. alstroemeriana is found in a continuum of re-association time and intensities with C. maculatum across the continent; in the Pacific Northwest, A. alstroemeriana can cause severe damage, resulting in some cases in complete defoliation. Studies in biological control and invasion biology have yet to determine whether plants re-associated with a significant herbivore from the area of indigeneity increase their chemical defense investment in areas of introduction. In this study we compared the secondary chemistry of C. maculatum in three locations in the U.S. (New York, Washington and Illinois) where C. maculatum experiences different levels of herbivory by A. alstroemeriana. We conducted an in situ sampling and a common garden experiment to determine the association between the intensity of the interaction, as measured by damage and chemical defense production. Total alkaloid production in C. maculatum was positively correlated with A. alstroemeriana herbivory levels. Individual plants with higher concentrations of monoterpenes and alkaloids received fewer eggs and experienced less damage by A. alstroemeriana suggestive of a preference on the part of the insect for plants with lower levels of chemical defense. These results suggest that A. alstroemeriana may act as a selective agent for C. maculatum and prolonged reassociation may increase toxicity of this noxious weed in its introduced range.