All intrauterine devices (IUDs) that have been tested experimentally or clinically induce a local inflammatory reaction of the endometrium whose cellular and humoral components are expressed in the tissue and the fluid filling the uterine cavity. Depending on the reproductive strategy of the species considered and the anatomical features and physiologic mechanisms that characterize their reproductive system, the secondary consequences of this foreign body reaction can be very localized within the uterus, as in the rabbit, or widespread throughout the entire genital tract as in women or even systemic as in some farm animals. Levonorgestrel released from an IUD causes some systemic effects, but local effects such as glandular atrophy and stromal decidualization, in addition to the foreign body reaction, are dominant. Copper ions released from an IUD enhance the inflammatory response and reach concentrations in the luminal fluids of the genital tract that are toxic for spermatozoa. In the human, the entire genital tract appears affected due to luminal transmission of the noxa that accumulates in the uterine lumen. This affects the function and viability of gametes, decreasing the rate of fertilization and lowering the chances of survival of any embryo that may be formed, before it reaches the uterus. The bulk of the data indicate that if any embryos are formed in the chronic presence of an IUD, it happens at a much lower rate than in non-IUD users. The common belief that the usual mechanism of action of IUDs in women is destruction of embryos in the uterus is not supported by empirical evidence.