To elucidate the effect of ovarian steroids on the secretion of immunosuppressive factor(s) from endometrium, supernatants from human endometrial cultures with or without the addition of progesterone or estrogen were compared for their effects on mixed lymphocyte reaction and phytohemagglutinin-induced lymphocyte reactivity. The suppressive activities of supernatants from the proliferative endometria were significantly increased by the addition of progesterone into their explant cultures. The addition of both progesterone and estrogen was also effective in increasing the inhibitory degree of proliferative endometria but that of estrogen alone showed no influence. Supernatants from the secretory endometria had higher suppressive activities than those from proliferative ones and showed no change in suppressive activity by the addition of ovarian steroids. The concentrations of progesterone in supernatants were too low to inhibit immune reactivity. These findings suggest that exogenous or endogenous progesterone may indirectly play an important role in the release of immunosuppressive factor(s) from human endometrium.