Angiotensin II (ANG) promotes cell proliferation and angiogenesis as well as being a potent vasoconstrictor. The cellular distribution of renin, ANG and its receptors in the endometrium has yielded useful information about the possible role of the renin-angiotensin system in cyclic menstruation. In the early proliferative phase, intense ANG-like immunostaining was detected in stroma and glandular epithelia, whereas in the late secretory phase, maximal immunoreactivity was localized in the perivascular stromal cells around the endometrial blood vessels. Quantitative receptor autoradiographic studies demonstrated that the human endometrium contains predominantly ANG type 2 receptor (AT2), with a relatively low expression of ANG type 1 receptor (AT1) and a novel non-AT1/non-AT2 ANG recognition site. AT receptors displayed cyclic changes, and the highest renin concentration was detected in the late secretory phase prior to menstruation. After long-term Norplant treatment, an increase in ANG-like immunoreactivity was observed in endometrial stroma and glandular epithelia, while in hyperplastic endometrium, ANG-like immunoreactivity decreased compared with normal cyclic endometria. The pattern of ANG immunostaining in endometria from patients with irregular menstruation was markedly different from that detected in normal endometrium. Normal function of the renin-angiotensin system in endometrium may be necessary for regular cyclic menstruation, and alterations in the distribution of ANG and/or the activity of its receptors are likely to be involved in dysfunctional uterine bleeding.