Objective: To identify unique cultural variables for African Americans that might limit the effectiveness of behavioral interventions in clinical trials. Design: Focus group discussions lasting 90 minutes. Setting: Outpatient, clinical research center. Patients: Twenty-six African-American men and women, who completed the screening process but were ineligible for the PREMIER study, participated in six focus group sessions. PREMIER is a multicenter, randomized clinical trial that studies the effects of three different lifestyle interventions designed to reduce blood pressure without medication. Measurements and main results: Participants used a value sort of cultural characteristics to select items that make them unique as African Americans. The following seven themes were consistently identified: 1) extensive use of nontraditional support systems; 2) general mistrust of European Americans; 3) African Americans' being undervalued as human beings and members of American society; 4) effective use of improvisation; 5) uneven playing field as a result of persistent discrimination; 6) preservation of a unique ethnic identity; 7) socioeconomic status as a major influence and predictor of behaviors. Conclusions: Cultural variables can affect African-American perceptions of the feasibility of certain behavior modifications as health interventions and their perceptions of clinical research. Using these themes, investigators can design trials and interventions that capitalize on certain cultural variables and avoid strategies that conflict with others. The identification of such cultural characteristics unique to African Americans may help to enhance the outcomes achieved by African Americans in clinical trials, improving the generalizability of results from behavior modification research.