Clues to the deliberate rather than a natural origin of a disease outbreak include the following: Cases of diseases not usually seen in the geographic area Unusual distribution of cases among segments of the population Significantly different attack rates between those inside and those outside buildings Separate outbreaks in geographically noncontiguous areas Multiple simultaneous or serial outbreaks of different diseases in the same population Unusual routes of exposure (eg, inhalation) Zoonotic disease occurring in humans rather than in animals Zoonotic disease occurring first in humans and then in its typical vector Zoonotic disease arising in an area with a low prevalence of the typical vector for the disease Unusual severity of disease Unusual strains of infectious agents Failure to respond to standard therapy Epidemiologic investigation of cases and cooperation with law-enforcement resources are crucial, as is risk communication to the general public.