It has been suggested that estrogen-progestagen therapy may be useful in preventing bleeding from gastric angiodysplasia, a vascular lesion similar to that described in portal-hypertensive gastropathy. In this study we assessed the effects of estrogen-progestagen therapy on gastric microcirculation and systemic and splanchnic hemodynamics in portal-hypertensive and sham-operated rats. One week after the surgical procedure (partial portal vein ligation or sham surgery), animals were given an intramuscular injection of a slow-release preparation of estrogen-progestagen or its vehicle. Two weeks later, gastric mucosal blood flow was measured by means of hydrogen gas clearance, a morphometrical analysis of gastric mucosal blood vessels was performed and systemic and splanchnic hemodynamics were evaluated with a radiolabeled-microspheres technique. In portal-hypertensive rats, estrogen-progestagen therapy induced a significant reduction in gastric mucosal blood flow, number of blood vessels and relative area of vessels. Similar changes, although of lesser magnitude, were achieved with estrogen or progestagen given separately and with the low dose of combined estrogen-progestagen. Estrogen-progestagen treatment also induced significant reductions in portal pressure and portocollateral resistance without changing systemic or splanchnic hemodynamics. In contrast, estrogen-progestagen treatment did not induce changes in any of the parameters studied in sham-operated rats. We conclude that long-term estrogen-progestagen therapy reduces the gastric hyperemia, increased mucosal vessel density and portal pressure in portal-hypertensive rats. (Hepatology 1994;20:1261–1270).