Summary:Although most children with AIDS have acquired HIV from their mothers, transmission from an HIV-infected mother to her infant is neither uniform nor currently predictable. With the rapid worldwide spread of HIV infection, particularly into women of child-bearing age, definition of the risk factors associated with maternal transmission is essential to develop and deliver intervention therapy that might impact on the devastating spread of AIDS. To promote research defining the risk factors of HIV transmission from mother to infant, an international workshop was held on January 17–18, 1992, in Siena, Italy. Epidemiology, immunology, virology, and health issues associated with maternal HIV transmission were actively discussed by participants. Current information from the literature and new data available from laboratories formed the basis for the consensus opinions developed at the meeting. Wide differences (10–39%) in HIV transmission seen at different geographic sites may be explained by multiple risk factors. The timing of transmission of HIV from mother to fetal, newborn, or breast-fed infants may be further complicated by viral burden and other cofactors. There are intriguing suggestions that the immunological status of the mother may be influential in preventing or reducing HIV transmission. But this appears to be interrelated with the HIV viral burden and health status of the mother and in turn her likelihood to transmit HIV to her offspring. The infecting “inoculum” may be low and/or selective because of biological barriers that favor reduced transmission with good health of the mother and the absence of other infectious diseases.