We investigated an immunologic mechanism that might explain the apparent "tolerant" state of the mother during pregnancy. Cellular-immune reactivity in vitro to paternal alloantigens was demonstrated in multigravid women by production of lymphocyte migration inhibitory factor. Serum from normal multigravid women contained a factor that blocked production of migration inhibitory factor by maternal lymphocytes to paternal antigens in a specific manner. The blocking factor was an IgG antibody whose activity was removed by absorption with paternal lymphocytes but not with pooled human platelets. We tested the biologic importance of this blocking factor in women who have difficulty maintaining a normal term pregnancy. Our observations indicate that women who experience idiopathic spontaneous abortions produce lymphocyte migration inhibitory factor to paternal alloantigens, but their serums lack the blocking factor. The presence of the serum blocking factor during pregnancy may contribute to the success of the fetus as an allograft.