A study has been made of granulated metrial gland (GMG) cells and adjacent layer I cytotrophoblast in the labyrinthine placenta of the mouse. In those cellular associations in which both cell types appeared healthy with the light microscope examination with the electron microscope identified features which may form part of the early stages in the interaction which can occur between GMG cells and some layer I trophoblast. These included microvillous processes from each cell forming an interdigitating netork, a polarization of mitochondria in a GMG cell with interdigitating microvilli, platelets, and some GMG cells which appeared to form a specialized cell junction with a small lymphocyte. The latter observation indicates that a tripartite functional relationshp may exist between lymphocytes, GMG cells and layer I labyrinthine trophoblast.In a quantiative analysis of GMG cells in the maternal blood spaces of placentae no significant differences in the numbers of GMG cells present in these spaces or involved in an interaction with layer I labyrinthine trophoblast were detected between inbred and outbred pregnancies. These results suggest that histocompatibility antigens are not significant factors in determining the frequency of interactions between GMG cells and trophoblast.