We studied the effect of intrauterine administration of levonorgestrel (LNG) on the ultrastructure of the endometrium. Twenty-one endometrial biopsy specimens, collected from nine fertile women during normal menstrual cycles and after 1, 3 or 6 months of use of a levonorgestrel-releasing intrauterine contraceptive system (LNG IUS), were studied using transmission and scanning electron microscopy. During the 6 month exposure to LNG IUS, changes took place in the endometrium. The glandular epithelial cells became lower. The junctional complexes between epithelial cells remained unchanged, whereas the lateral microvillar interdigitations became more prominent. The basal lamina under the epithelium became wavy but remained uniform and practically uninterrupted; only solitary epithelial cell protrusions through the basal lamina were seen. The stromal cells were largely decidualized. We conclude that in parallel with the generally known cellular effects, the use of the LNG IUS results in distinct changes in the basal lamina between the endometrial epithelial and stromal cells. The especially well-developed and uninterrupted basal lamina may be involved in the mechanism of the LNG IUS-induced endometrial suppression. Furthermore, the complex intercellular junctions between the epithelial cells, normally loosening around the time of implantation, persist during the local administration of levonorgestrel. This may have a pivotal role in the contraceptive effect of the LNG IUS.