When an emergency swine disease outbreak, such as foot-and-mouth disease (FMD), occurs, it will be necessary to rapidly and humanely depopulate and dispose of infected and susceptible pigs to limit viral replications and disease spread. Methods other than handling individual pigs will be required to achieve the necessary rapidity. Suitable and practical on-farm methods will require depopulating large numbers of pigs at a time outside confinement buildings. The process must be easily implemented with readily available materials and equipment, while providing for the safety and well-being of personnel. Carbon dioxide gas (CO2) is the means of choice, and this study analyzed the methods and requirements for delivering the gas into large volume truck bodies, corrals, dumpsters or other such chambers that may be used. The issues studied included: How the gas should be introduced to achieve the needed spatial distribution; whether plenums are required in the chambers; and the importance of sealing all chamber cracks and edges except around the top cover to limit CO2 dilution and leakage. Analysis was done using computational fluid dynamics (CFD) software, and primary results were verified experimentally. The CFD findings and experimental results are compared, and recommendations are discussed.