The role of the renin-angiotensin system in the development of hypertension was studied by infusing an angiotensin II analog, 1-Sar, 8-Ile angiotensin II, in women with toxemia and women on estrogen-containing oral contraceptives or estrogen treatment. In 3 of 4 women who developed hypertension on oral contraceptives or estrogen treatment, the blood pressure was reduced with the infusion of 1-Sar, 8-Ile angiotensin II. In 3 women who remained normotensive on oral contraceptives or estrogen treatment, the blood pressure was not reduced, although there was no significant difference in plasma renin activity (PRA) between the women who developed hypertension and those who remained normotensive on oral contraceptives. In 6 pregnant women who developed hypertension, the blood pressure increased remarkably with the infusion of 1-Sar, 8-Ile angiotensin II, although PRA was increased significantly in all of them. In these women, however, sodium excretion was less than that in normal pregnant women. In 4 normal pregnant women, the blood pressure remained unchanged or increased slightly, and PRA was almost similar to that of women who developed hypertension. The above results suggest that increased PRA in women who developed hypertension whilst on estrogen-containing oral contraceptives or estrogen treatment is more closely related to the development or maintenance of hypertension than that in pregnant women who develop hypertension, although there remains a possibility that the response of blood pressure to 1-Sar, 8-Ile angiotensin II in pregnant women who develop hypertension is influenced by sodium retention.