In response to two jet aircraft crashing into and causing the collapse of the 110-storied World Trade Center (WTC) towers and the subsequent destruction of nearby portions of lower Manhattan, the New York City Department of Health (NYCDOH) immediately activated its emergency response protocol, including the mobilization of an Emergency Operations Center. Surveillance, clinical, environmental, sheltering, laboratory, management information systems, and operations were among the preestablished emergency committees. Because of its proximity to the WTC site, an emergency clinic was established at NYCDOH for triage and treatment of injured persons. NYCDOH focused its initial efforts on assessing the public health and medical impact of the attack and the resources needed to respond to it such as the care and management of large numbers of persons injured or killed by the crash; subsequent fire and building collapse; the health and safety of rescue workers; the environmental health risks (e.g., asbestos, smoke, dust, or chemical inhalation); other illnesses related to the disruption of the physical infrastructure (e.g., waterborne and foodborne diseases); and mental health concerns. Despite the evacuation and relocation of NYCDOH's headquarters, the department continued essential public health services, including death registration.