The under-representation of racial/ethnic minorities among medical research participants has recently resulted in mandates for their inclusion by the National Institutes of Health (NIH). Therefore, there is a need to determine how history, attitudes, cultural beliefs, social issues, and investigator behavior affect minority enrollment in medical research studies. From January 1998 to March 1999, 179 African-American and white residents of the Detroit Primary Metropolitan Statistical Area (PMSA) participated in a mail and telephone survey designed to examine impediments to African-American participation in medical research studies. Chi-square tests were performed to assess differences between the study groups using the Survey Data Analysis Program (SUDAAN). Eighty-one percent of African Americans and 28% of whites had knowledge of the Tuskegee Study (p=< 0.001). Knowledge of the Tuskegee Study resulted in less trust of researchers for 51% of African-Americans and 17% of whites (p= 0.02). Forty-six percent of African-Americans and 34% of whites indicated that their knowledge of the study would affect future research participation decisions (p= 0.25). Of these, 49% of African-Americans and 17% of whites would not be willing to participate in future medical research studies (p= 0.05). This study confirms the need for medical researchers to confront the issue of the Tuskegee Study and its continuing impact on African-Americans' trust of medical research studies.