For the past decade, the Food and Agriculture Organization of the United Nations has been working toward eradicating rinderpest through vaccination and intense surveillance by 2012. Because of the potential severity of a rinderpest epidemic, it is prudent to prepare for an unexpected outbreak in animal populations. There is no immunity to the disease among the livestock or wildlife in the United States (US). If rinderpest were to emerge in the US, the loss in livestock could be devastating. We predict the potential spread of rinderpest using a two-stage model for the spread of a multi-host infectious disease among agricultural animals in the US. The model incorporates large-scale interactions among US counties and the small-scale dynamics of disease spread within a county. The model epidemic was seeded in 16 locations and there was a strong dependence of the overall epidemic size on the starting location. The epidemics were classified according to overall size into small epidemics of 100 to 300 animals (failed epidemics), epidemics infecting 3,000 to 30,000 animals (medium epidemics), and the large epidemics infecting around one million beef cattle. The size of the rinderpest epidemics were directly related to the origin of the disease and whether or not the disease moved into certain key counties in high-livestock-density areas of the US. The epidemic size also depended upon response time and effectiveness of movement controls.