OBJECTIVE: To investigate in vivo and in humans the mechanisms and kinetics of vagina-to-uterus distribution. DESIGN: Controlled clinical study. SETTING: Volunteers in an academic research environment. PATIENT(S): Six postmenopausal women undergoing transabdominal hysterectomy were selected.Intervention(s): Women received 0.2 mL of (99m)Tc-pertechnetate vaginally. In three patients the cervical canal was previously sealed by means of surgical glue. Six postmenopausal women who had received (99m)Tc-pertechnetate intravenously for a thyroid scintigraphy were considered as a control. MAIN OUTCOME MEASURE(S): Radioactivity was assessed every 30 minutes for 6 hours in the pelvis and in body regions where (99m)Tc-pertechnetate normally accumulates (thyroid, salivary glands, and stomach). RESULT(S): Uterine activity appeared after 60 minutes and peaked between 120 to 210 minutes. These same times were observed in the patients who had a sealed cervix. Thyroid uptake appeared after 180 minutes and peaked between 210 and 330 minutes. Uterine uptake did not occur in any of the intravenous patients; their thyroid uptake was rapid, appearing after 30 minutes. CONCLUSION(S): Preferential vagina-to-uterus distribution, at least in postmenopausal women, is not simply due an intracanalicular passage but is mediated by absorption of substances and probably by a countercurrent transfer mechanism.