CDC has begun distribution of a new-generation smallpox vaccine, ACAM2000™ (Acambis, Inc., Cambridge, Massachusetts), to civilian laboratory personnel, the military, and state public health preparedness programs. ACAM2000 is a live, vaccinia virus smallpox vaccine that was licensed for use in the United States by the Food and Drug Administration in August 2007 (1).* ACAM2000 will be replacing Dryvax® smallpox vaccine (Wyeth Pharmaceuticals, Inc., Marietta, Pennsylvania) because of withdrawal of the Dryvax license. ACAM2000 is a live vaccinia virus derived from plaque purification cloning from Dryvax. The safety data available from the ACAM2000 clinical trials indicate a similar safety profile to Dryvax.