Embryo implantation has been demonstrated to depend on specific lymphocyte populations within the uterine cavity. Intrauterine devices (IUD) exert their contraceptive action by prevention of embryo implantation via presently still unknown mechanisms. Therefore, mononuclear cell populations from mice uteri which either contained silastic or copper (Cu) IUD fragments or were sham-operated were evaluated, utilizing monoclonal antibodies against specific cell markers. Uterine horns, bearing IUD fragments, were significantly heavier than sham-operated horns. In Cu-IUD animals this effect extended even into the non-treated contralateral horn. The total number of lymphoid cells in IUD-bearing horns was significantly higher than in shamoperated horns. This observation was also made in non-treated contralateral Cu-IUD horns but not in contralateral horns of silastic-IUD-treated animals. Significant differences in percentages as well as absolute number of various lymphoid cell populations were noted between IUD-treated and sham-operated animals. Again, the effect was more pronounced in Cu-IUD-treated animals and extended in those animals into the contralateral horn. IUD-containing horns also demonstrated a significantly increased number of mast cells, with Cu-IUDs again resulting in a significantly more pronounced effect in both treated and contralateral horns. Sham-operated mice achieved a 67% pregnancy rate in both uterine horns. In contrast, IUD-treated animals demonstrated a significantly reduced pregnancy rate with silastic IUD fragments (15% and 30% for treated and contralateral horn, respectively) and a 0% pregnancy rate for Cu-IUD-treated animals (in either horn).