Maternal-to-fetal transmission of the murine lactate dehydrogenase-elevating virus (LDV) has been previously shown to be regulated by maternal immunity as well as gestational age. For the present study, the role of maternal immunity in placental and umbilical cord virus protection was studied, and virus targeting of umbilical cord and fetal macrophages was correlated with expression of the F4/80 macrophage phenotypic marker. The results showed that LDV-infected macrophages appeared in umbilical cord by 24 h post-infection of pregnant mice, and some LDV-infected macrophages displayed the F4/80 phenotype. This potential reservoir of virus for the fetus was inhibited by passive immunization of pregnant mice with IgG anti-LDV antibodies, which rapidly concentrated in the placenta and umbilical cord. Probing of umbilical cord cells with antibodies directed at MHC genetic markers demonstrated the presence of both maternal and fetal cells in umbilical cords. A strong developmental correlation was observed between fetal F4/80 expression and LDV susceptibility, at about 13.6 days of gestation. These results demonstrate immune suppression of free and cell-associated virus in umbilical cord, thus defining a potentially important mechanism for immune protection of the fetus from transplacental virus infection. The results also clarify the developmental basis for fetal susceptibility to LDV infection. Copyright 2002 Published by Elsevier Science Ltd.