Insertion of an IUD into the uterine cavity is associated with an inflammatory cellular response of the endometrium, which initially is common to all IUDs as the endometrial tissue reacts to the presence of a foreign body. Other types of morphologic modifications specific to different types of IUDs are then observed and may be important in understanding the mode of action of the device and in explaining bleeding patterns associated with IUDs. The endometrial response to inert and copper IUDs is quite similar. The part of the endometrial surface in contact with an inert or copper IUD loses its outer layer of epithelial tissue, exposing the lower layer of basal membrane. The rest of the epithelium in contact with the IUD appears flattened, and some epithelial cells lose their microvilli. Ultrastructural studies have demonstrated a reduction in number of ciliated cells and an alteration of the secretory activity of the surface epithelium and to a lesser degree of the glandular epithelium in reaction to the IUD. Diffuse interstitial bleeding with migration of erythrocytes between the interepithelial spaces has frequently been seen. Ultrastructural studies clearly show that inert IUDs induce lesions and later secondary modifications of the surface epithelium, the superficial vascular epithelium, the glandular epithelium, and to a lesser extent other endometrial cells. With copper IUDs, surface erosions of endometrial epithelium are seen, with much more cellular destruction and signs of bleeding in the part in contact with the copper. As with inert IUDs, the adjacent basal membrane is usually intact. A notable finding in the endometrium is the existence of microthrombosis of stromal capillaries, especially in the portion exposed to the copper. There appears to be a direct relationship between the amount of copper and the degree of ultrastructural modification. The effects of progesterone-releasing IUDs on the surface epithelium, the glands, the stroma, and the vascularization vary as a function of the dose and type of progestin, the proximity of the tissue and the part of the IUD treated, and the time elapsed since insertion.