The specific renin (EC 3.4.99.19) activity in the adrenal of spontaneously hypertensive rats was determined by a method that is capable of distinguishing renin from nonspecific renin-like activity ofproteases by using specific antibody to renin. The renin level in the adrenals of adult spontaneously hypertensive rats with established hypertension was found to be 6-8 times as high as that of the normotensive control Wistar-Kyoto strain. The large difference in the adrenal renin level was observed even in 3-wk-old rats in which hypertension had not yet developed. The adrenal renin level was increased by bilateral nephrectomy in both the hypertensive and normotensive strains. A larger quantity of renin was found in the adrenal cortex than in the medulla, and the difference between the hypertensive strain and the normotensive strain was more prominent in the cortex than in the medulla. These results suggest possible involvement of adrenal renin in the development and in the early maintenance phase of hypertension in this animal model of human essential hypertension by affecting the adrenocortical or adrenomedullary activity, or both.The etiology of hypertension in spontaneously hypertensive rats (SHR) (1) has been of great interest in view of its resemblance to essential hypertension in humans. Elevated levels of dopamine f3-hydroxylase (EC 1.14.17.1) activity in plasma (2), mesenteric vessels, and adrenals (3) and decreased levels of dopamine ,3-hydroxylase activity (3) and norepinephrin (4) in the noradrenergic regions of the brain observed before the development of hypertension indicate a significant role of neurogenic factors in the initiation ofthe hypertension ofthis animal model (5). The aberrations in the levels of these neurogenic substances are no more than 2-fold. On the other hand, normal or subnormal levels of plasma renin (EC 3.4.99.19) have indicated the lack of a causative role for the renin-angiotensin system in spontaneous hypertension (6)(7)(8)(9)(10).However, the recent finding that the angiotensin-converting enzyme inhibitor, captopril (D-3-mercapto-2-methylpropanoyl-L-proline), normalizes the blood pressure of patients with essential hypertension and that of the SHR (11, 12) suggests a possible role of the renin-angiotensin system in this type of essential hypertension. Because the plasma level of renin activity is not increased and because captopril is known to be taken up by tissues (13), such a renin-angiotensin system may exert its effect by its local function.Although the earlier observation of a renin-like enzyme within various extrarenal tissues (14) may have been mostly due to cathepsin D (EC 3.4.23.5) (15, 16), we have demonstrated the presence ofspecific renin, which is inhibitable by antibodies to renin, in various tissues of hogs (17) and rats (18). A particularly high renin activity was found in the rat adrenal (18). Therefore, in an attempt to assess the possible role of the tissue renin-angiotensin system in the peripheral system of spontaneous hypertension, we have comp...