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In Pennsylvania on February 16, 2006, a New York City resident collapsed with rigors and was hospitalized. On February 21, the Centers for Disease Control and Prevention and the New York City Department of Health and Mental Hygiene were notified that Bacillus anthracis had been identified in the patient's blood. Although the patient's history of working with dried animal hides to make African drums indicated the likelihood of a natural exposure to aerosolized anthrax spores, bioterrorism had to be ruled out first. Ultimately, this case proved to be the first case of naturally occurring inhalational anthrax in 30 years. This article describes the epidemiologic and environmental investigation to identify other cases and persons at risk and to determine the source of exposure and scope of contamination. Because stricter regulation of the importation of animal hides from areas where anthrax is enzootic is difficult, public healthcare officials should consider the possibility of future naturally occurring anthrax cases caused by contaminated hides. Federal protocols are needed to assist in the local response, which should be tempered by our growing understanding of the epidemiology of naturally acquired anthrax. These protocols should include recommended methods for reliable and efficient environmental sample collection and laboratory testing, and environmental risk assessments and remediation.