We evaluated the willingness of clients at a large urban sexually transmitted diseases (STD) clinic in the southeastern United States to participate in future trials of preventive vaccines for HIV type 1 (HIV-1). A single trained interviewer administered an oral survey instrument to STD clinic clients over a 4-week enrollment period. The participants were 167 randomly selected clients (90 men and 77 women), most of whom were young, African-American heterosexuals. Risk behaviors for HIV-1 infection were highly prevalent. Overall, 67% of clients expressed willingness to consider participation in an HIV-1 vaccine trial. By univariate analysis, prior HIV-1 testing was significantly associated with willingness to participate (P = 0.04). Multivariate analysis revealed that female gender (P = 0.05) and prior HIV-1 testing (P = 0.03) were significant predictors of willingness to participate.