On February 21, 2006, the Pennsylvania Department of Health (PDOH) reported to CDC and the New York City (NYC) Department of Health and Mental Hygiene (DOHMH) a case of inhalation anthrax in a man who resided in New York City. This report summarizes the joint epidemiologic and environmental investigation conducted by local, state, and federal public health, animal health, and law enforcement authorities in Pennsylvania and NYC to determine the source of exposure and identify other persons who were potentially at risk.