As a naturally occurring bovine pathogen, bovine respiratory syncytial virus (BRSV) engages with the innate and adaptive immune responses of cattle in an evolutionarily meaningful fashion. Therefore, studying viruses in their native hosts, rather than in non-native hosts, is more likely to authentically reflect the pathogenesis of natural infection. Experimental infection of calves with BRSV provides an important tool for investigating mechanisms of pathogenesis and immunity to RSV infection, and can also be used for evaluating new strategies for the prevention and treatment of RSV infection in both cattle and man. Here, we present materials and methods used to propagate BRSV, infect calves with BRSV, and analyze samples from BRSV-infected calves.