To clarify the possible immunologic functions of the endometrium before implantation, supernatants from explant cultures of human endometrial tissues were examined for effects on mixed lymphocyte reaction and phytohemagglutinin M-stimulated cultures. Supernatants obtained from both proliferative and secretory phase endometria showed significant dose-related suppressive effects; the suppressive activity of secretory phase endometria was higher than that of proliferative phase endometria. On the other hand, no inhibitory effect was identified in supernatants from similar cultures of peritoneum and omentum, while supernatants of fallopian tubes showed slight suppressive activity. These results suggest the existence of soluble nonspecific immunosuppressive factor(s) released from human endometrium (especially during the secretory phase), and imply that these factor(s) may exert an important role in protecting the fertilized ovum from maternal rejection.