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Simulation models are important for investigating foot-and-mouth disease (FMD) introduction scenarios and testing the potential effectiveness of control programs. To incorporate disease spread via domestic livestock and wildlife populations, a multi-model approach has been used to simulate potential FMD outbreaks in a region of Texas. Within the study region - a 9-county area (24,525 sq.km) of southern Texas, bordering Mexico - the distribution of cattle and feral pigs was estimated based on land use and vegetation characteristics. A geographic automata model of FMD spread between feral pig herds (1 km2 grid) was used to initiate the outbreak. During each simulated day of spread, we identified cattle herds (represented as either points or polygons) that may have been infected. We then used, separately, two spread models of FMD in domestic species to simulate an FMD outbreak in cattle herds in the study region. Initial simulations of this multi-model system based on introduction of infection into five randomly selected feral pig herds as input to the two spread models resulted in a typical outbreak that lasted 1-2 R. Sanson / Preventive Veterinary Medicine 81 (2007) 213-223 221 months and could affect about 100 cattle herds. The multi-epidemiologic modeling framework is currently being integrated with livestock transportation, carcass disposal and economic models to create a scalable and generic decision support system.