African Americans are less likely than European Americans to participate in biomedical research. Researchers often attribute nonparticipation to the "Tuskegee effect." Using critical qualitative analysis of focus group data, we examined the public's use of the Tuskegee Study of Untreated Syphilis (TSUS) to discuss biomedical research. Our participants articulated three primary themes in relation to TSUS: 1) that TSUS made them suspicious about biomedical research; 2) that other values had to weigh against concerns about TSUS; and 3) that African Americans could take steps to resolve their concerns about TSUS. African Americans were more likely to discuss TSUS than were European Americans. African Americans did not use TSUS to express simple fear. African Americans suggested issues other than TSUS that influence the decision to participate in research. African Americans indicated specific reforms that would increase participation in research. We discuss how a better understanding of African Americans' use of TSUS can enhance research participation and allay concerns about "another Tuskegee."