Effective, feasible interventions to prevent perinatal transmission of HIV-1 in developing nations are an urgent necessity. Scientific issues of concern include a need to identify other effective antiretroviral agents; to define the shortest effective course of therapy; to assess interventions other than antiretroviral agents; and to investigate interventions that may reduce HIV-1 transmission via breastfeeding. Sound scientific design is fundamental to all research studies. Ethical standards must guide such studies and include the necessity that the problem studied be a health priority in the host country; that the highest standard of care attainable in the country be assured to participants; that the health-care resources of the country not be harmed; that the informed consent of participants be obtained; and that a process of discussion ensure that a successful intervention will be considered for implementation. There are circumstances in which a no-antiretroviral comparison may be ethically justified.