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Department of defense and homeland security analysts are increasingly using multi-agent simulation (MAS) to examine national security issues. This paper summarizes three MAS national security studies conducted at the Naval Postgraduate School. The first example explores equipment and employment options for protecting critical infrastructure. The second case considers non-lethal weapons within the spectrum of force-protection options in a maritime environment. The final application investigates emergency (police, fire, and medical) responses to an urban terrorist attack. There are many potentially influential factors and many sources of uncertainty associated with each of these simulated scenarios. Thus, efficient experimental designs and computing clusters are used to enable us to explore many thousands of computational experiments, while simultaneously varying many factors. The results illustrate how MAS experiments can provide valuable insights into defense and homeland security operations.