Further, the methods used and the persons invited to participate as research subjects must be selected so as to minimize materialization of risks and maximize the benefits. Subjects who participate must do so voluntarily with full knowledge of the possible risks and benefits, and confidentiality must be maintained. Particular difficulties arise in clinical trials targeting populations outside the developed world. Ethical principles applicable to biomedical research are difficult to satisfy in the current context of AIDS vaccine clinical trials. The difficulties go beyond typical problems of delaying the research until institutional review board approval is obtained, predicting unforeseeable harms, or spreading potential benefits and risks unevenly between controlled and experimental subjects. If existing experimental vaccines do not satisfy our ethical obligations to protect experimental research subjects, we have a variety of choices available to us including deferring clinical trials until an animal model is found; changing our code of ethics to allow the use of humans instead of animals in research; or determining more clearly the minimum prerequisites required in animal studies, in vitro studies, or computer models, before vaccines are tried on humans. 47 references.