The role of air travel in the global spread of influenza has been the subject of a significant body of research, but this question has yet to be explored within the U.S. The goal of this research is to explore whether knowledge of U.S. air travel patterns and volumes leads to better forecasting of epidemics. We report the results of a series of simulations for the 1998–1999 through 2000–2001 influenza seasons using a standard compartmental model coupled with air transportation data. These preliminary results suggest that air travel may play an important role in the spread of annual influenza within the U.S., particularly in cities with large air travel volumes.