Angiotensin-converting enzyme (ACE) inhibitors have been designed to reduce the generation of angiotensin II, i.e., to block the renin-angiotensin system. Interestingly, there exists a considerable dissociation between the time course of ACE inhibition and that of blockade of the renin-angiotensin system. Due to the greatly improved methodology used to estimate the degree of ACE inhibition in vitro and in vivo, it has become evident that the compensatory increase in renin levels in response to ACE inhibition is the key factor determining the degree and duration of blockade of the renin-angiotensin system resulting from ACE inhibition. A better understanding of these relationships would seem to be useful in determining duration of action and particularly the optimal dose of any ACE inhibitor.