The United States Congress directed the Department of Justice to conduct an exercise engaging key personnel in the management of mock chemical, biological, or cyberterrorist attacks. The resulting exercise was called "TOPOFF," named for its engagement of top officials of the United States government. This article offers a number of medical and public health observations and lessons discovered during the bioterrorism component of the exercise. The TOPOFF exercise illuminated problematic issues of leadership and decision-making; the difficulties of prioritization and distribution of scarce resources; the crisis that contagious epidemics would cause in health care facilities; and the critical need to formulate sound principles of disease containment. These lessons should provoke consideration of future directions for bioterrorism planning and preparedness at all levels of government and among the many communities and practitioners with responsibilities for national security and public health.