Angiotensin II blockade with sarcosine 1-alanine 8-angiotensin II (saralasin, P-113) was done in 40 studies of 20 hypertensive patients. Eleven of 12 patients with a depressor response to angiotensin II blockade had significant renovascular or renal disease, and nine of 10 had renal vein renin measurements that lateralized to the abnormal kidney. In contrast, none of the patients without a depressor response had renovascular abnormalities. Plasma renin activity was usually high in responders to saralasin (18 ng/ml-h) when compared with nonresponders (0.5 ng/ml-h). In these studies a correlation between the fall in blood pressure and the rise in plasma renin activity during angiotensin II blockade was observed while renin was unchanged in the absence of depressor responses. In two renovascular renin-dependent hypertensive patients, treatment with diuretics induced severe hyperreninemia and a rise in blood pressure that was reversed by sodium loading.