OBJECTIVE: To examine potential disparities in willingness to be vaccinated against smallpox among different U.S. racial/ethnic groups. DESIGN: Cross-sectional survey using an experimental design to assess willingness to be vaccinated among African Americans compared to whites according to 2 strategies: a post-exposure “ring vaccination” method and a pre-exposure national vaccination program. SETTING: Philadelphia County district courthouse. PARTICIPANTS: Individuals awaiting jury duty. MEASUREMENTS: We included 2 scenarios representing these strategies in 2 otherwise identical questionnaires and randomly assigned them to participants. We compared responses by African Americans and whites. MAIN RESULTS: In the pre-exposure scenario, 66% of 190 participants were willing to get vaccinated against smallpox. In contrast, 84% of 200 participants were willing to get vaccinated in the post-exposure scenario (P=.0001). African Americans were less willing than whites to get vaccinated in the pre-exposure scenario (54% vs 77%; P=.004), but not in the post-exposure scenario (84% vs 88%; P=.56). In multivariate analyses, overall willingness to undergo vaccination was associated with vaccination strategy (odds ratio, 3.29; 95% confidence interval, 1.8 to 6.1). CONCLUSIONS: Racial disparity in willingness to get vaccinated varies by the characteristics of the vaccination program. Overall willingness was highest in the context of a post-exposure scenario. These results highlight the importance of considering social issues when constructing bioterror attack response plans that adequately address the needs of all of society's members