The Tuskegee Syphilis Study continues to cast its long shadow on the contemporary relationship between African Americans and the biomedical community. Numerous reports have argued that the Tuskegee Syphilis Study is the most important reason why many African Americans distrust the institutions of medicine and public health. Such an interpretation neglects a critical historical point: the mistrust predated public revelations about the Tuskegee study. This paper places the syphilis study within a broader historical and social context to demonstrate that several factors have influenced--and continue to influence--African American's attitudes toward the biomedical community.