The impact of a bioterrorist attack depends on the specific agent or toxin used, the method and efficiency of dispersal, the population exposed, the level of immunity in the population, the availability of effective postexposure and/or therapeutic regimens, and the potential for secondary transmission. The comparative impact of three biologic agents--Bacillus anthracis (anthrax), Brucella melitensis (brucellosis), and Francisella tularensis (tularemia)--were analyzed and the benefits of systematic intervention with the costs of increased disease incidence were compared. Results showed that the economic impact of a bioterrorist attack could range from $477.7 million per 100,000 persons exposed in the brucellosis scenario to $26.2 billion per 100,000 persons exposed in the anthrax scenario. Low estimates were consistently used for all factors directly affecting costs. Early implementation of a prophylaxis program after an attack is essential. Delay in starting a prophylaxis program is the single most important factor for increased losses (reduced net savings). Although implemented at different times in a threat-attack continuum, both attack prevention measures and prophylaxis programs are forms of preventive medicine. The ability to rapidly identify persons at risk would also have a significant impact on costs. This finding provides an economic rationale for preparedness to rapidly and accurately identify the population at risk and reduce unnecessary prophylaxis costs. This model provides an economic rationale for preparedness measures to both reduce the probability of an attack and increase the capability to rapidly respond in the event of an attack. The larger portion of a preparedness budget should be allocated to measures that enhance rapid response to an attack. These measures would include developing and maintaining laboratory capabilities for both clinical diagnostic testing and environmental sampling, developing and maintaining drug stockpiles, and developing and practicing response plans at the local level. 2 figures, 6 tables, 22 references