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The grasslands of eastern Colorado are inhabited by two species of rattlesnakes, the Prairie Rattlesnake (Crotalus viridis) and the Desert Massasauga Rattlesnake (Sistrurus tergeminus edwardsii). An array of rodent species, both native and introduced, also occupy these grasslands, and serve as a varied prey base for the previously listed rattlesnakes. Predator-prey interactions in this system gain an additional level of complexity due to the presence of venoms, a chemical arsenal possessed by both rattlesnakes to incapacitate their prey. Rodents in other systems have demonstrated resistance to snake venoms, and there is potential for a similar dynamic to be present in eastern Colorado. This project aimed to characterize resistance to Prairie Rattlesnake and Desert Massasauga Rattlesnake venoms in a suite of wild rodents, using two field sites to better understand the role of co-occurrence of predator-prey partners. Resistance to venoms was explored using in-vivo techniques (LD50 assays on test populations of wild-collected rodents) and in-vitro assays (serum metalloprotease inhibition). Rodent serum was further analyzed using affinity chromatography to isolate potential venom-resistance proteins. Results provide a community-level view of venom resistance and indicate that resistance to venoms is variable across predator-prey species pairings. Additionally, this study characterized the diet of the Prairie Rattlesnake, a taxon for which little dietary data has been collected. The Prairie Rattlesnake occupies a broad latitudinal distribution, spanning a climatic gradient, and is believed to be a dietary generalist. We analyzed prey remains from preserved museum specimens and compiled a list of prey items consumed. This dataset was further used to detect feeding variation as a result of latitude, ontogeny, and seasonality. No apparent feeding differences occurred as a result of latitude, a strong signature of dietary ontogeny was absent in the dataset, and snakes did not exhibit prolonged foraging in warmer regions. These studies elucidate the trophic biology of snakes on their ecosystems, an area of study that at present remains poorly understood. Results indicate that rattlesnakes have the potential to exert tremendous selective pressures upon the prey communities they interact with, and thus may impact prey species over evolutionary timescales. Understanding the underpinnings of snake foraging and resistance to snake venoms allows us to contextualize better the role of snakes in natural systems.