The model was designed to meet the following objectives: describe the spread of smallpox through a susceptible population; readily accommodate changes in input values; examine the impact of quarantine and vaccination, alone and in combination, on the spread of smallpox; and estimate the number of doses of smallpox vaccine that should be stockpiled as part of readiness plans. The model describes four disease stages: incubating, prodromal (preeruptive), overtly symptomatic, and no longer infectious. The most important policy implications from the model results are: (1) delay in intervention will be costly, dramatically increasing the total number of cases; (2) postrelease intervention should be a combination of quarantine and vaccination; (3) planning requires not only an appreciation of how many persons may be infected initially, but also an understanding of the likely rate of transmission; and (4) a stockpile of approximately 40 million doses of vaccine should be adequate. The article concludes that a large part of preparing a public health response to smallpox as a bioterrorist weapon must involve educating policymakers and the public as to why quarantine is necessary and why relying solely on mass immunization may not be the magic bullet that some are hoping it will be. Notes, figures, tables, references