Worldwide clinical trials are in progress or are being planned to evaluate different interventions aimed at reducing transmission of human immunodeficiency virus (HIV) from mother to infant. Several new therapeutic agents will soon be the focus of clinical trials to evaluate their safety for pregnant women and their infants and to test their efficacy in preventing perinatal transmission. Identification of the factors that influence the timing and mechanism of perinatal HIV transmission is essential to the assessment of interventions to reduce transmission. An international workshop was held on June 3-6, 1993, in Siena, Italy, to review what is known about the risk factors, timing, and mechanisms of HIV type 1 (HIV-1) transmission from mother to infant during gestation, birth, and lactation. Several possible interventions were compared with respect to their mechanism of action, their dependence upon the mode and timing of perinatal HIV transmission, and their suitability for incorporation into trials, alone or in combination, in various parts of the world. Obstetrical interventions such as caesarian section or use of a virucidal vaginal lavage during labor, administration of antiretroviral drugs to mother and/or infant, as well as active and/or passive immunization were discussed. The role of breast-feeding in perinatal HIV infection and in the trials was also evaluated. Because the ability to enroll pregnant, HIV-infected women in trials is limited, it is essential that proposed trials be carefully evaluated for adequacy of the sample size, appropriateness of the type of intervention to the particular population of women to be enrolled, and feasibility of the intervention. Worldwide coordination of perinatal intervention trials is essential to prevent duplication, allow the optimal use of human and financial resources, and ensure the most rapid possible evaluation and implementation of means to prevent pediatric HIV infection.