Although we are increasingly aware that an understanding of evolution is critical to all biological fields and to scientific literacy, evolution remains a challenge in the classroom. Here we present a hands-on, inquiry-based classroom activity to study host-parasite coevolution. Coevolution is the reciprocal evolution of interacting species. It is pervasive, diverse, and rapid. Instruction in coevolution is therefore an excellent way to teach students evolutionary principles. In the described game, students take on the role of either host or parasite, and they use playing cards to act out reciprocal selection. Students collaborate to collect data on the change in frequency of host and parasite genotypes (card suits) through time. They use these data to conduct an independent test of the prediction that hostparasite coevolution maintains genetic variation. The game is suitable for students ranging from upper-level high school through college. We include detailed instructions, discussion topics, and simple modifications to extend the game to additional topics. This is a fun, active, and simple exercise to introduce students to the complex topic of hostparasite coevolution. Moreover, the game emphasizes infectious diseases as major selective forces, a fascinating topic for today's students.