To study the expression of aquaporin-2 (AQP2) in human endometrium.Prospective clinical study.Hospital-based unit for gynecology and obstetrics and research laboratories.Healthy women with proven fertility who were divided into four groups according to LH peak.Endometrial biopsies were obtained from 34 women on cycle days LH+4 to LH+14.Localization of AQP2 in human endometrium during normal cycle using immunohistochemistry, verification of AQP2 expression through detection of AQP2 mRNA in reverse transcriptase-polymerase chain reaction (RT-PCR), detection of pinopodes using scanning electron microscopy, and confirmation of AQP2 on pinopodes in confocal microscopy.Immunostaining of AQP2 is present in the luminal and glandular epithelium but not in the stroma. Some vessels stained positive for AQP2. When present, pinopodes stained positive, which was confirmed using confocal microscopy. A significant increase in staining intensity was seen in the glandular and luminal epithelium during the mid and late luteal phases of the cycle. The presence of AQP2 in human endometrium was also confirmed by RT-PCR.AQP2 is present in the human endometrium. The expression of AQP2 appears to be cycle dependent and suggests a role for AQP2 in implantation, edema, and/or menstruation.