To clarify the characterization and immunologic mechanisms of endometrial extract as a suppressive factor in tissues of the implantation site, the effects of endometrial extract and IgG on mitogen-stimulated cultures of lymphocytes from human peripheral blood were investigated. The inhibitory activity of endometrial extracts was observed to be augmented markedly in the secretory phase of the menstrual cycle as compared to the proliferative phase. Secretory endometrial extract, at a concentration of 0.6 mg protein/ml, caused 50% suppression of PHA-induced lymphocyte blastogenesis (PHA-BL). Column fractionation of endometrial extract on a Sephadex G-200 column showed a profile with three peak fractions and demonstrated that the 2nd peak fraction was mainly responsible for the suppression of PHA-BL. The 2nd peak fraction was shown to contain IgG by the method of immunodiffusion with anti-human IgG. The 2nd peak fraction from which IgG was removed with affinity chromatography caused significant depression of PHA-BL. Furthermore, the Fc fraction of IgG showed marked suppression compared to the F(ab')2 fraction. From these results, we suggest the possibility of an endogenous substance containing IgG as a suppressive factor which is implicated in the suppression of T cell function. The Fc fragment seemed to be the major fraction possessing such suppressive activity.