The first compounds used to block the renin-angiotensin system were polypeptide antagonists of angiotensin II, administered parenterally. Subsequently, orally active angiotensin converting enzyme inhibitors were developed which were generally well tolerated, and were effective in the treatment of hypertension and congestive heart failure. Today they are well established as therapeutic agents. Nevertheless, the search continues for more specific therapeutic agents such as orally active renin inhibitors and angiotensin II antagonists, and accurate biochemical methods must be available to assess their efficacy. All approaches trigger a considerable compensatory rise in renin secretion which tends to counteract the blocking effect of these compounds. Hence all agents, but particularly the renin inhibitors, must have a good bioavailability and a high affinity in order to overcome the effect of the compensatory renin secretory response. As yet, it is too early to predict whether the potentially more specific renin inhibitors or angiotensin II antagonists will replace the present widely used angiotensin converting enzyme inhibitors.