Aortic homogenates contain proteolytic enzymes which will release angiotensin I (AI) from renin substrate. Some of these are active at low pH and are probably unrelated to renin. Renin-like activity in the rat measured at the optimum pH of 6.5 is altered in parallel with plasma renin in a wide variety of situations. The two diverge only in non-steady state situations. Studies have therefore been carried out after bilateral nephrectomy and after the injection of renal renin into nephrectomized rats. In each case aortic renin-like activity was cleared much more slowly than plasma renin, and the blood pressure change was related to aortic renin-like activity rather than to plasma renin. The blood pressure response to the converting enzyme inhibitor teprotide was also related to the former rather than the latter. Immunofluorescent studies of the aorta and the intrasplenic arteries from rats injected with mouse renin showed that renin was taken up predominantly into the media and persisted at this site. Thus, the uptake of renal renin from plasma by both large and small arteries is probably an important step in the physiology of the renin-angiotensin system and mediates renin-induced changes in peripheral resistance and blood pressure. However, we have no evidence for the hypothesis that selective accumulation of renin in the resistance vessel walls causes hypertension when circulating levels of renin are normal.