The hypothesis that hormones produced by the placenta contribute to immunosuppression during pregnancy is an attractive one. In order partially to evaluate this hypothesis, we utilized the Migration Inhibition Factor (MIF) Assay, which is an in vitro model of delayed hypersensitivity in that presensitized lymphocytes stimulated by antigen release a glycoprotein (MIF) which inhibits the normal migration of macrophages. The effect of placental hormones on this model of cellular immunity was tested using the direct and indirect MIF assays in pre-immunized guinea pigs. Estradiol (1-50 microgram/ml), progesterone (1-50 microgram/ml) and commercial grade or chromatography-purified hCG (1000-5000 IU/ml) did not affect normal macrophage migration and also failed to suppress production of MIF by guinea pig lymphocytes stimulated with antigen. None of the hormones either enhanced or suppressed macrophage response to preformed MIF. The results indicate that these hormones do not suppress lymphocyte reactivity as assessed by the production of lymphokines or the target cell response to the mediator. The reported effects of steroid hormones and crude hCG on other models of cellular immunity are discussed.