Conventional radioimmunoassay techniques demonstrated in the aortic wall a renin-like activity which is derived from plasma but has a longer half-life than plasma renin. Blood pressure elevation after renin injection into nephrectomized rats correlates better with aortic renin than with plasma renin. Vascular and other extrarenal tissue can also synthesize renin. Using a ribonuclease protection technique for the detection of renin messenger RNA we have been able to demonstrate that a wide variety of extrarenal tissues contain the renin message. In at least two of these, the brain and the liver, renin messenger RNA levels are unaffected by changes in dietary salt or by changes in systemic blood pressure. Functional studies using isolated human resistance vessels also demonstrate the presence of renin-like activity by a contractile response to added renin substrate. It is suggested that extrarenal tissues therefore contain renin-like activity derived both from uptake and from local synthesis. These systems may be regulated in different ways and may carry out different functions.