Cytomegalovirus (CMV) is one of the most frequent causes of intrauterine-acquired infection in the human species. However, very little is known about the pathophysiology of the transplacental transmission of the virus from the mother to the fetus. In this study, the passage of CMV across the human term placenta, and the susceptibility of the human term trophoblast to infection with CMV was investigated. In vitro dual perfusion of human term placental lobules was performed. In five experiments the perfused tissue was exposed to high titres (10(4)-10(6) 50 per cent tissue culture infective doses) of CMV AD169 for up to 9.5 h. Monitoring included placental functional parameters, and virus titres in the perfused tissue, and in the fetal and maternal circuit. Immunocytochemistry with a monoclonal antibody against CMV immediate early antigen was used to search for placental infection. CMV AD169 did not cross the placenta even during many hours of perfusion, up to 9.5 h, and with exposure to high virus titres. No infected placental cells were detected by immunocytochemistry, although the virus cultures from perfused tissue samples were positive. The perfused human term placenta and the term trophoblast in vitro form an effective barrier to cell-free CMV AD169.