Abstract Respiratory syncytial virus (RSV) is the number one cause of lower respiratory infections in children. Although most children are infected with RSV in their first year of life, 40% have severe disease suggesting a genetic component in addition to age. This collaborative project aims to identify genetic determinants associated with RSV infectivity during the neonatal period. Recombinant inbred strains of mice such as the BXD family have been extensively typed for both genetic polymorphisms (5 million variants) and a wide range of phenotypes, including influenza and other pathogens. Here, we infected different BXD strains with RSV at five days of age and evaluated pulmonary viral load. We show a difference in viral burden in the lungs of neonatal mice between different BXD strains, suggesting a role for genetic variation in RSV infectivity. Therefore, we have a novel system to identify genetic loci involved in the development of RSV disease. These results will be critical in the development of specific antivirals and vaccines against RSV.