Essentially all new cases of human immuno-deficiency virus (HIV) infection in infants and young children occur as a consequence of exposure to HIV eitherin utero, intrapartum or postpartum during breast feeding. Currently it is estimated that the majority of vertical transmission of HIV occurs at or near the time of birth. Based on what is known about the biology of perinatal HIV transmission, the HIV burden of the mother, effectiveness of her immune response and that of her fetus/infant and the integrity of the placental “barrier” are likely to play important roles in this process. The role of impaired immunologic control of HIV is gaining recognition as a potential key element in the pathophysiology of perinatal HIV transmission. In most studies to date, advanced maternal disease and low CD4 lymphocyte count have been associated with increased risk of vertical HIV transmission. In addition some studies have indicated that low maternal titers of antibodies to certain V3 loop epitopes may have a similar effect on vertical transmission. Cellular immune responses, which are known to play an important role in host defense against HIV, appear to be impaired in infants after exposure to HIV, especially those responses involving the development of cytotoxic lymphocytes. Mounting evidence suggests that enhancement of humoral and/or cellular immune responses in pregnant women and exposed infants is a logical and potentially feasible approach to interruption of perinatal transmission (an approach similar to that utilized for perinatally acquired hepatitis B virus infection). Studies are now in progress to assess HIV hyperimmune globulin and envelope HIV vaccines in pregnant woman and HIV-exposed infants.