Endometrial samples from 64 women using different types of IUDs were used to study the ultrastructural changes of the human endometrium as influenced by nonmedicated and copper devices, using SEM and TEM in an attempt to explain the physiological mechanism of their actions. The absence of cytoplasmic macro-apocrine secretory granules with copper devices and their defective separation with nonmedicated IUDs support the theory that the IUD interferes with the carbohydrate metabolism and secretory function of the endometrial cells. It also indicates that IUDs may function through the interference with the blastocyst-endometrial interaction and blastocyst survival. The change in the intrauterine environment due to the absence of normal secretion may also affect sperm capacitation and/or the acrosomal reaction, with subsequent failure of fertilization. The absence of ciliated cells at the site of copper IUD contact zone and their defective ciliation away from it in the presence of normal steroid function may indicate an effect of the copper ions on the estrogen receptors. The asynchronous development of the endometrium and blastocyst mechanism of IUD function was not supported in this study. The occurrence of intermenstrual bleeding with IUDs is governed by 2 factors: 1) the pressure exerted by the IUD causing endothelial vascular injury and release of erythrocytes into endometrial stroma; and 2) the increased stromal hydrostatic pressure which acts as a force against the basal lamina and epithelial integrity. This was proven by the loss of normal microvillous pattern of the endometrial cells even away from the copper IUD, which support the rigidity of the cellular membranes.