The field of “coevolutionary studies” is the origin of many evocative stories in evolutionary biology, as well as a demonstration of the value of studying the ecological interactions of whole organisms and populations. This field exploded after the publication of “Butterflies and Plants: A Study in Coevolution,” a 1964 paper co-authored by entomologist Paul Ehrlich and botanist Peter Raven. However, this paper argues that the foundation for “Butterflies and Plants” was laid in the previous decades, in the work of economic entomologists, crop-plant breeders, and insect physiologists. Using the work of an influential insect physiologist, Gottfried S. Fraenkel, this paper examines the prehistory of coevolutionary studies, showing that practical research on insect feeding in the 1940s and 1950s transformed plant chemicals into active biological molecules—causal forces modeled on hormones. Insect physiologists were the first to study the effects of these molecules on insects. Yet, rather than redefining insect-plant interactions in terms of reductionist molecular causation, they sought a more integrative explanation. Not only did these insect biologists see plants as active participants in their ecological and evolutionary landscapes, but they also came to see evolutionary history as the “ raison d’être ” of plant molecules and insect feeding behavior. This paper expands our understanding of the generative role that physiology and molecular methods played in the development of concepts and practices in evolutionary biology. Furthermore, it contributes to a growing literature that undermines the historical division between proximate and ultimate causation in biology.