Biochemical and bioassay evidence has proved the existence of tissue RAA systems although their function has not been satisfactorily defined. There are two sources of tissue renin: uptake from plasma and local synthesis. The uptake system has been demonstrated in arterial tissue. Retention of renin can be demonstrated in the aortic wall and the presence of renin at this site is closely correlated with the persistent elevation of blood pressure. Renin gene expression can be demonstrated in several organs such as the liver, brain and arterial wall, although the function of renin or pro-renin at these sites is unknown. Intracellular angiotensin II receptors have been identified that play a role in regulating gene expression. In addition to raising vascular tone, angiotensin II generated in this way could have a trophic action upon cardiac and vascular structures. There is now very strong evidence in favour of the extrarenal RAA system having a pathogenetic role in some forms of hypertension. Renin gene polymorphisms co-segregate with blood pressure in some genetic models, despite normal or low plasma renin and incorporation of an additional mouse renin gene construct into the rat genome produces severe hypertension despite suppression of renal renin.