People wounded during bombings or other events resulting in mass casualties or in conjunction with the resulting emergency response may be exposed to blood, body fluids, or tissue from other injured people and thus be at risk for bloodborne infections such as hepatitis B virus, hepatitis C virus, human immunodeficiency virus, or tetanus. This report adapts existing general recommendations on the use of immunization and postexposure prophylaxis for tetanus and for occupational and nonoccupational exposures to bloodborne pathogens to the specific situation of a mass casualty event. Decisions regarding the implementation of prophylaxis are complex, and drawing parallels from existing guidelines is difficult. For any prophylactic intervention to be implemented effectively, guidance must be simple, straightforward, and logistically undemanding. Critical review during development of this guidance was provided by representatives of the National Association of County and City Health Officials, the Council of State and Territorial Epidemiologists, and representatives of the acute injury care, trauma, and emergency response medical communities participating in the Centers for Disease Control and Prevention's Terrorism Injuries: Information, Dissemination and Exchange project. There recommendations contained in this report represent the consensus of US federal public health officials and reflect the experience and input of public health officials at all levels of government and the acute injury response community.