BACKGROUND: The problems of underenrollment and selective enrollment may undermine AIDS vaccine trials. If prospective study subjects' stated willingness to participate (WTP) in hypothetical vaccine trials predicts future enrollment, then measuring WTP before recruitment may enhance the enrollment in, and ethics of, such trials. METHODS: We prospectively studied changes over an 18-month period in the stated WTP in, and knowledge of, a hypothetical AIDS vaccine trial among 610 Philadelphia residents at high risk for HIV infection. Of these people, 499 were subsequently recruited to participate in an actual, phase II AIDS vaccine trial. We used multivariable logistic regression and the area under the receiver-operating characteristic (ROC) curve to model predictors of actual enrollment. RESULTS: Actual enrollment rates were 8.3%, 6.8%, 15.8%, and 29.0% among those who had initially said they were "definitely not," "probably not," "probably," and "definitely" willing to participate, respectively (p =.006). The area under the ROC curve was 0.65, indicating a modest ability of stated WTP to differentiate those who enroll from those who do not. Knowledge of basic vaccine trial concepts, though unrelated to enrollment, increased over an 18-month period with repeated education sessions (p <.0001), whereas stated WTP declined over this same period (p <.0001). CONCLUSION: Although other factors not captured by stated WTP may also influence future enrollment, prospectively assessing stated WTP may augment the validity of the informed consent process, help prevent underenrollment, and clarify the population from which the study sample is drawn.