MHC class II molecules are not normally expressed on the cell surface of placental cells. This absence of class II molecules is assumed to be of importance for mammalian reproduction, since such expression is likely to increase the risk of harmful anti-placental immune responses. The present study was aimed to clarify whether post-transcriptional events prohibit proper cell surface expression of MHC class II molecules in cell lines of placental origin. The murine trophoblast cell line SM9-1 as well as the human choriocarcinoma-derived cell line JEG-3 were transiently co-transfected with MHC class II Aq a and b genes under the control of viral promoter systems. The transfected cells were stained for surface expression of MHC class II and assayed for antigen presentation in vitro. Only a small proportion of the transfected murine SM9-1 cells showed detectable class II cell surface expression, which made functional studies of this cell line difficult. The transfected JEG-3 cells, however, showed a high proportion of cells with distinct surface expression of murine class II Aq molecules and the antigen presentation assays revealed T cell activation upon addition of processed antigen, but not with unprocessed antigen. These results show that ectopic MHC class II gene transcription can result in cell surface expression of immunohistochemically detectable MHC class II on cells of placental origin. The fact that murine class II molecules could be expressed in a functional manner on human JEG-3 cells also strongly suggests that proper accessory gene activities are not essential for obtaining surface expression.