It has been shown that development of mouse blastocysts, transplanted to ectopic sites in mice, can be inhibited by preimmunizing the host against transplantation antigens of the donor strain. Similar inhibition can be produced by repeated transplants of blastocysts to extrauterine sites in one host. The present investigation reports findings on the nature of this inhibition. Histological examination of recipient organs from hosts presensitized with either transplantation antigens or blastocysts reveals that the principal effect in both cases is upon trophoblast differentiation and proliferation. This effect is subsequently reflected in the size of the haemorrhagic nodule produced in the host organ. Transplantation immunity appears more effective in this respect than blastocyst-elicited sensitivity. It is concluded that trophoblast expresses weak histocompatibility antigenicity and that an immune response of some kind can be elicited by ectopically situated blastocysts. The immunological factor responsible for the observed progressive diminution of growth has not been determined but does not appear to be cell mediated.