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Protocols for mass antibiotic prophylaxis against anthrax were under development in New York City beginning in early 1999. This groundwork allowed the city's Department of Health to rapidly respond in 2001 to six situations in which cases were identified or anthrax spores were found. The key aspects of planning and lessons learned from each of these mass prophylaxis operations are reviewed. Antibiotic distribution was facilitated by limiting medical histories to issues relevant to prescribingdoi:10.3201/eid0906.030118 pmid:12781998 fatcat:5zfmi7wzuzeuhigc47glrzqoii