The effects of estrogen treatment upon plasma renin parameters were determined in groups of male rats 1, 6, and 12 hr after administration of a single injection of 100 μg ethinylestradiol, and after more prolonged treatment for 2 and 5 days with 100 μg ethinyl—estradiol daily. In the latter groups, the response to furosemide administration was also evaluated. Measurements of plasma renin activity (PRA), plasma renin concentration (PRC) and renin substrate (PRS) were performed by radioimmunoassay of angiotensin I generated in plasma incubated alone (PRA), with an excess of rat renin substrate (PRC) and with an excess of rat renin (PRS). The most notable result of these experiments was the rapid onset of the estrogen—induced rise in circulating renin substrate, which was significantly elevated as early as 6 hr after a single injection of estradiol. This rise was accompanied by an early increase in PRA, which remained elevated for 2 days during continued estrogen treatment and fell to slightly below normal levels by the sixth day. No change in PRC was observed during the first 12 hr of treatment; a slight fall occurred by the second day, and a highly significant decrease to less than one—half of the control value was present at the sixth day. These results illustrate the rapidity with which elevation of PRS, and subsequently PRA, may occur following estrogen administration, and are in general similar to the changes observed in women during oral contraceptive therapy. In both species, the estrogen—induced rise in plasma renin substrate has been shown to enhance the plasma renin activity, this effect being demonstrable in the rat only during the first few days of treatment, and is followed by a marked reduction of renin secretion and plasma renin concentration. (Endocrinology92: 1382, 1973)