Recent evidence suggests that local immunoregulation may prevent rejection of the placenta by the mother. This local immunoregulation may also compromise the response to placental infection. Listeria monocytogenes infection in 121 pregnant mice and 1,050 fetoplacental units was examined and the kinetics of bacterial growth in various maternal and fetal tissues were determined. A subset of pregnant mice developed overwhelming placental listeria infections. Pregnancy did not impair the maternal immune response in the liver and spleen. Pregnant mice without placental infection had numbers of listeria equivalent to nonpregnant controls and mice immunized during pregnancy had significantly less listeria than nonimmunized controls. The secondary response in immunized pregnant mice had no effect on the development of placental infection and the histologic features of placental infection were distinct from those in other organs. Our data suggest that an ineffective local immune response may contribute to the pathogenicity of listeria for the placenta.