The purpose of this study was to examine the contribution of the subfornical organ to the chronic hypertension produced by intravenous angiotensin II infusion in rats. Male rats were instrumented with permanent arterial and venous catheters and housed in metabolism cages for daily measurement of arterial pressure, heart rate, water intake, water balance, and urinary electrolyte excretion. Angiotensin II was infused intravenously at a rate of 10 ng/minute for 5 consecutive days, preceded by 2 control days, and followed by 2 recovery days. Normal rats with an intact subfornical organ (n = 7), and rats with an electrolytic lesion placed such that greater than 80% of the subfornical organ was destroyed (n = 9), were studied using this infusion protocol. An additional group of eight rats did not receive angiotensin II, and, thus, served as a time control. Both groups of rats receiving angiotensin II exhibited significant elevations in arterial pressure during the 5-day hormone infusion period, but pressure in rats with subfornical organ lesions (delta 23-29 mm Hg) was increased significantly more than that of intact rats (delta 14-20 mm Hg). Water intake was significantly increased on the 3rd, 4th, and 5th days of angiotensin II infusion only in rats with lesions in the subfornical organ. In contrast to previous studies showing that an intact subfornical organ is required for normal pressor and drinking responses to acute elevations in circulating angiotensin II in the rat, the current experiments indicate that the presence of the subfornical organ actually inhibits these same responses during more chronic increases in plasma angiotensin II levels.